The Effect of Reproductive Factors on Breast Cancer Presentation in Women Who Are BRCA Mutation Carrier / 한국유방암학회지

PURPOSE: Germline mutations in the BRCA1 and BRCA2 genes confer increased risks for breast cancers. However, the clinical presentation of breast cancer among women who are carriers of the BRCA1 or BRCA2 (BRCA1/2 carriers) mutations is heterogenous. We aimed to identify the effects of the reproductive histories of women with the BRCA1/2 mutations on the clinical presentation of breast cancer. METHODS: We retrospectively analyzed clinical data on women with proven BRCA1 and BRCA2 mutations who were recruited to the Korean Hereditary Breast Cancer study, from 2007 to 2014. RESULTS: Among the 736 women who were BRCA1/2 mutation carriers, a total of 483 women had breast cancers. Breast cancer diagnosis occurred at significantly younger ages in women who experienced menarche at ≤14 years of age, compared to those who experienced menarche at >14 years of age (37.38±7.60 and 43.30±10.11, respectively, p<0.001). Additionally, the number of full-term pregnancies was significantly associated with the age of diagnosis, especially in women with the BRCA2 mutation. The prevalence of advanced stages (stage II or III vs. stage I) of disease in parous women was higher than in nulliparous women (68.5% vs. 55.2%, p=0.043). This association was more pronounced in women with the BRCA2 mutation (hazard ratio, 2.67; p=0.014). CONCLUSION: Our results suggest that reproductive factors, such as the age of onset of menarche and the presence of parity, are associated with the clinical presentation patterns of breast cancer in BRCA1/2 mutation carriers.

Two Cases of Rhabdomyolysis after E xcessive E xercise

Rhabdomyolysis is a syndrome involving the breakdown of skeletal muscle causing myoglobin and other intracellular proteins and electrolytes to leak into the circulation. There are various causes of acute rhabdomyolysis in childhood, such as direct trauma to muscle, muscle necrosis from ischemia, inflammation in muscle, or exposure to drugs and toxins. The most-important complication of this disorder is acute renal failure (ARF). However, the contributing factors to the development of ARF in children with rhabdomyolysis remain obscure. We report two cases of rhabdomyolysis after excessive exercise.

The Correlation between the Severity of Hypoxic Ischemic Encephalopathy and the Development of Acute Renal Failure in Asphyxiated Neonates

PURPOSE: We performed this study to determine the incidence of acute renal failure(ARF) in birth asphyxia and to correlate the severity of asphyxia and hypoxic-ischemic encephalopathy (HIE) and ARF in asphyxiated neonates. METHODS: Data was retrospectively collected from the medical records of 33 patients with neonatal asphyxia and of 33 neonates with no asphyxia. On the basis the 5-minute Apgar score, the asphyxiated neonates were further grouped into mild(6 or 7), moderate(4 or 5), and severe asphyxia(3 or less). Asphyxiated neonates with HIE were staged by the Sarnat and Sarnat scoring system. We compared serum creatinine, blood urea nitrogen, electrolytes, and urine output on day 3 of life and the incidence and severity of intraventricular hemorrhage(IVH) between each group. RESULTS: ARF occurred in 8(24.2%) asphyxiated neonates. Of these, 3(37.5%) were oliguric, while 1(10.0%) patient with mild asphyxia, 2(18.2%) of moderate asphyxia, and 5(41.7%) with of severe asphyxia had ARF(P>0.05). One(25%) patient with stage I HIE, 4(50%) with stage II HIE, and 3(75%) of HIE with stage III HIE developed ARF(P<0.01). There was no statistical correlation between the severity of asphyxia and HIE stage. One(7.7%) patient with grade 1 IVE, 0(0.0%) with grade 2 IVH, 2(66.7%) with grade 3 IVH, and 2(100.0%) with grade 4 IVH had ARF(P<0.01). Mortality was higher in asphyxiated neonates with ARF(P<0.05). There was no significant difference between the oliguric and non-oliguric renal failure. CONCLUSION: We found that the greater the degree of HIE, the higher was the incidence of ARF. Asphyxiated neonates with ARF had a poorer prognosis.

Differentiation of Hyperplastic from Metastatic Lymph Nodes Using a Lymph Node Specific MR Contrast Agent Gadofluorine M

PURPOSE: We wanted to evaluate the value of a lymph node specific MR contrast agent, Gadofluorine M, for the differentiation of hyperplastic and metastatic lymph nodes. MATERIALS AND METHODS: This study included thirty-one rabbits. In ten rabbits, an injection of egg yolk or feces of rat into the calf muscles induced hyperplasia of the lymph node. In sixteen rabbits, metastasis of the lymph node was induced by implantation of VX2 tumor. Five rabbits were normal control models. We acquired the T1-, T2-weighted and SPGR coronal imaging before enhancement with 1.5 T MR. After injection of Gadofluorine M (5 micromol/mL, total amount: 4 mL) interstitially into the interdigital skin fold of the hind limb, we acquired the SPGR coronal imaging at 15, 30, 60 and 90 minutes. We calculated the signal-to-noise ratios on the sequential images, and we recorded the number, size and location of the popliteal and iliac lymph nodes. Three readers assessed the state of the lymph nodes according to the pattern of enhancement: they were deemed hyperplastic nodes when totally enhanced and as metastatic nodes when there was no or partial enhancement. We also compared the imaging patterns with the histopathological results. RESULTS: Among the 26 hyperplasia- or metastasis-induced rabbits, two rabbits were excluded because of failure to be enhanced. Histopathologic evaluation of the 24 rabbits detected one hundred seventeen lymph nodes: forty-six lymph nodes in nine hyperplasia-induced rabbits and seventy-one (metastasis in twenty-eight) lymph nodes in fifteen metastasis-induced rabbits. Out of one hundred two lymph nodes that were larger than 5 mm in size, MR enabled us to detect one hundred one lymph nodes (99.1%). The means of sensitivity, specificity, and the positive and negative predictive values for the diagnosis of lymph node metastasis by three readers were 97.6% (82/84), 98.2% (215/219), 95.3% (82/86), and 99.1% (215/217), respectively (p < 0.05). CONCLUSION: Interstitial MR lymphography using Gadofluorine M showed excellent results in differentiating hyperplastic from metastatic lymph nodes.

Histiocytic Sarcoma of the Spleen: A Case Report and Review of the Literature

True histiocytic sarcoma is an extremely rare tumor. Its clinicopathological features are not clearly understood. Here, we report the first Korean case of primary splenic histiocytic sarcoma. A 64-year-old female having refractory thrombocytopenia, anemia and splenic mass was admitted to the hospital, and received splenectomy. Grossly, spleen was enlarged up to 18 x 13 x 8 cm and occupied with multinodular masses. Microscopically, the masses were composed of atyical large cells with abudant cytoplasm and vesicular nuclei with prominent hemophagocytosis. The tumor cells were CD68 (+), S-100 protein (-), CD21 (-), CD1a (-). After splenectomy, thrombocytopenia and anemia were corrected. However two months later the symptoms recurred, and the patient died 15 months after splenectomy. This case shared the common clinicopathologic features with the several previously reported cases in other countries, represented by splenic mass formation and prominent hemophagocytosis associated with thrombocytopenia and anemia, often leading to poor outcome.

ADENOMATOID ODONTOGENIC TUMOR: REPORT OF A CASE INVOLVING MAXILLARY SINUS

Methylation Status of Epstein-Barr Virus Major Latent Promoter C in NK/T-cell Lymphoma and Peripheral T-cell Lymphoma

BACKGROUND: Both the Natural killer/T-cell lymphoma (NKTL) and the peripheral T-cell lymphoma (PTCL) are relatively prevalent in the Asian population, and they are strongly associated with the Epstein-Barr virus (EBV). These two diseases have several common pathologic features, but show somewhat different clinical presentations. The critical point in terms of differentiating of these disease groups might be the impact of EBV in pathogenesis, and the variable gene expression of EBV regulated by a major latent C promoter (Cp). METHODS: We investigated 43 cases of NKTL and 30 cases of PTCL to evaluate EBV associated characteristics. EBV in situ hybridization was performed in all of the submitted cases. In the EBV positive cases, the methylation status of Cp which drives the expression of immunodominant viral nuclear protein, was examined by sensitive methylation specific PCR using paraffin embedded tissue. RESULTS: EBV was found in 70% (30/43) of NKTL and 43% (13/30) of PTCL. Nasal and gastrointestinal lymphomas were predominantly NKTL. All of the successfully amplified cases of EBV positive NKTL and PTCL were of methylated Cp status. CONCLUSIONS: The detection rate of EBV is high in NKTL, especially in the nasal area. The constantly methylated EBV Cp reflects the major role of Cp in regulating the EBV latency pattern and in helping EBV to avoid host immune system in both NKTL and PTCL.

Methylotion Analysis of p16/INK4A in Gastric Low-Grade Mucosa-Associated Lymphoid Tissue Lymphomas after Helicobacter pylori Eradication Therapy

BACKGROUND: Inactivation of p16 has been associated with promoter region hypermethylation in different types of malignancies, including non-Hodgkin's lymphomas (NHLs). This loss of p16 was found frequently in cases of mucosa-associated lymphoid tissue (MALT) lymphomas. Recent studies indicate that promoter hypermethylation is often an early event in tumor progression in the follow-up of NHLs. METHODS: To investigate the usefulness of p16 methylation in the diagnosis and follow-up of gastric low-grade MALT lymphomas, we analyzed methylation status of p16 using methylation-specific polymerase chain reaction methods in the sequential biopsy specimens of 13 patients with gastric low-grade MALT lymphomas undergoing Helicobacter pylori eradication therapy. RESULTS: Five of thriteen cases showed p16 hypermethylation upon diagnosis. In four of five methylation positive cases, abnormal methylation was detected in the specimen even after the treatment, although there were no histologic evidence of disease. This methylation disappeared in the later samples of two of the cases, and they have remained in complete remission. Immunohistochemically, the loss of p16 protein expression was detected in one of three methylation-positive cases, and in none of the methylation-negative cases. CONCLUSIONS: These results suggest that p16 methylation is relatively fequent in low-grade gastric MALT lymphomas, and it may have clinical applications in the management and follow-up of low-grade gastric MALT lymphomas.

Detection of Breast Cancer Micrometastases in Sentinel Lymph Nodes / 한국유방암학회지

PURPOSE: Axillary lymph node status is a powerful prognostic factor in breast carcinomas. However, patients without axillary lymph node metastases are not completely devoid of risk for relapse. Also, the axillary lymph node micrometastases significantly contribute to the selection of high-risk patients. Recently, sentinel lymph node (SLN) biopsy has been proposed as a potential alternative to full axillary lymph node dissection for staging breast carcinomas. To validate this hypothesis, we evaluated the distribution of occult metastases in sentinel and nonsentinel lymph nodes. METHODS: Twenty patients who had breast carcinomas and who underwent a SLN biopsy followed by an axillary lymph node dissection during March and July 2000 at Seoul National University Hospital were evaluated. Thirty SLNs devoid of metastasis, as determined by hematoxylin and eosin (H&E) staining, were evaluated for micrometastases by pan- cytokeratin immunohistochemistry (IHC) and reverse transcriptase polymerase chain reaction (RT-PCR) using Keratin 19 mRNA and MUC1 mRNA. Nonsentinel lymph nodes (NSLN) were also evaluated by pan-cytokeratin IHC. RESULTS: One out of the 30 SLNs (3.3%) had occult metastases which were identified by IHC and 4 out of the 30 SLNs (13.3%) had occult metastases which were identified by RT-PCR. NSLNs devoid of metastases by H&E staining proved to be free of micrometastases by IHC. CONCLUSION: IHC and RT-PCR are more sensitive methods for detecting micrometastases than conventional H&E stain-ing alone. If an SLN is tumor free by IHC or RT-PCR, we can assume that the remaining lymph nodes in the axilla are also tumor free, consequently, an SLN biopsy can bea substitute for axillary lymph node dissection.

Detection of Breast Cancer Micrometastases in Sentinel Lymph Nodes

PURPOSE: Axillary lymph node status is a powerful prognostic factor in breast carcinomas. However, patients without axillary lymph node metastases are not completely devoid of risk for relapse. Also, the axillary lymph node micrometastases significantly contribute to the selection of high-risk patients. Recently, sentinel lymph node (SLN) biopsy has been proposed as a potential alternative to full axillary lymph node dissection for staging breast carcinomas. To validate this hypothesis, we evaluated the distribution of occult metastases in sentinel and nonsentinel lymph nodes. METHODS: Twenty patients who had breast carcinomas and who underwent a SLN biopsy followed by an axillary lymph node dissection during March and July 2000 at Seoul National University Hospital were evaluated. Thirty SLNs devoid of metastasis, as determined by hematoxylin and eosin (H&E) staining, were evaluated for micrometastases by pan- cytokeratin immunohistochemistry (IHC) and reverse transcriptase polymerase chain reaction (RT-PCR) using Keratin 19 mRNA and MUC1 mRNA. Nonsentinel lymph nodes (NSLN) were also evaluated by pan-cytokeratin IHC. RESULTS: One out of the 30 SLNs (3.3%) had occult metastases which were identified by IHC and 4 out of the 30 SLNs (13.3%) had occult metastases which were identified by RT-PCR. NSLNs devoid of metastases by H&E staining proved to be free of micrometastases by IHC. CONCLUSION: IHC and RT-PCR are more sensitive methods for detecting micrometastases than conventional H&E staining alone. If an SLN is tumor free by IHC or RT-PCR, we can assume that the remaining lymph nodes in the axilla are also tumor free, consequently, an SLN biopsy can bea substitute for axillary lymph node dissection.

Detection of Breast Cancer Micrometastases in Sentinel Lymph Nodes / 한국유방암학회지

PURPOSE: Axillary lymph node status is a powerful prognostic factor in breast carcinoma. However, patients without axillary lymph node metastases are not completely devoid of risk for relapse. And the axillary lymph node micrometastases will significantly contribute to the selection of high-risk patients. Recently, sentinel lymph node(SLN) biopsy has been proposed as a potential alternative to full axillary lymph node dissection for staging breast carcinoma. To validate this hypothesis, the distribution of occult metastases in sentinel and nonsentinel lymph node was evaluated. MATERIALS & METHODS: Twenty patients who underwent SLN biopsy followed by axillary lymph node dissection during March and July 2000 due to breast carcinoma at Seoul National University Hospital were evaluated. Thirty SLN devoid of metastasis by hematoxylin and eosin(H&E) staining were evaluated for micrometastases by Pan-cytokeratin immunohistochemistry(IHC) and Reverse Transcriptase Polymerase Chain Reaction(RT-PCR) using Keratin 19 mRNA and MUC1 mRNA. Nonsentinel lymph nodes(NSLN) were also evaluated by Pan-cytokeratin IHC. RESULTS: One out of 30 SLNs(3.3%) had occult metastases by IHC and 4 out of 30 SLNs(13.3%) had occult metastases by RT-PCR. NSLNs devoid of metastases by H&E stain were proved to be free of micrometastases by IHC. CONCLUSION: IHC and RT-PCR are sensitive methods for detecting micrometastases than conventional H&E staining alone. If SLN is tumor free by IHC or RT-PCR, we can assume that the remaining lymph nodes in the axilla are also tumor free and SLN biopsy can be a substitute for axillary lymph node dissection.

Colorectal adenocarcinoma as a second malignant neoplasm following rhabdomyosarcoma of the urinary bladder: a case report

Following improvements in therapy for childhood malignancies, the striking increase in survival rate over the past 30 years has led to the increase risk of developing second malignant neoplasms (SMNs). We report a case of colorectal carcinoma as a SMN, following treatment for rhabdomyosarcoma. The patient was diagnosed with rhabdomyosarcoma of the urinary bladder at his age of three years, and developed adenocarcinoma in the colon 13 years later. Histologic examination of the surgical specimen revealed adenocarcinoma involving the rectosigmoid area with radiation colitis in its background. The tumor cells showed strong immunoreactivity for p53 protein, suggesting the role of irradiation and p53 mutation in carcinogenesis. This case emphasizes the need for dose observation in survivors of early childhood malignancies treated with radiation and multiagent chemotherapy.

Colorectal adenocarcinoma as a second malignant neoplasm following rhabdomyosarcoma of the urinary bladder: a case report

Following improvements in therapy for childhood malignancies, the striking increase in survival rate over the past 30 years has led to the increase risk of developing second malignant neoplasms (SMNs). We report a case of colorectal carcinoma as a SMN, following treatment for rhabdomyosarcoma. The patient was diagnosed with rhabdomyosarcoma of the urinary bladder at his age of three years, and developed adenocarcinoma in the colon 13 years later. Histologic examination of the surgical specimen revealed adenocarcinoma involving the rectosigmoid area with radiation colitis in its background. The tumor cells showed strong immunoreactivity for p53 protein, suggesting the role of irradiation and p53 mutation in carcinogenesis. This case emphasizes the need for dose observation in survivors of early childhood malignancies treated with radiation and multiagent chemotherapy.

Correlation between Clinical Outcome and Proliferation Index in Diffuse Large B-Cell Lymphoma

The diffuse large B-cell lymphoma category of the Revised European American Classification of Lymphoid Neoplasms (REAL) encompasses different morphologic lymphoma subtypes in a single entity, especially the diffuse large cell (DLC) and the immunoblastic (IBL) subtypes by Working Formulation (WF). The aim of this study is to determine the influence of the morphologic subdivision within this category with respect to clinical outcome and proliferative index using Ki-67 immunostainig combined with image analysis. We retrospectively reviewed 74 patients from 1990 to 1996, who were diagnosed with diffuse large B-cell lymphoma. All cases were reclassified according to REAL and Working Formulation (WF), and Ki-67 immunostaining was performed in all the cases. Fifty-eight cases (78.4%) were classified as DLC and 16 cases (21.6%) as IBL, according to WF. Twenty one cases (28.4%) showed nodal involvement and 53 cases (71.6%), extranodal involvement. All cases were found to display a variable degree of nuclear Ki-67 staining. A proliferative index of 50% or higher identified a group of patients (77%) who had poor clinical results. Overall survival was significantly reduced in these patients displaying high Ki-67 associated proliferative index compared to those with a low proliferative index (p=0.007). 5-year survival estimates were 93% in the low proliferative index group and 55% in the high proliferative index group. A multivariate regression analysis incorporating commonly used clinical prognostic factors confirmed the independent effect of proliferation index on survival. Moreover, all of the 16 IBL cases showed Ki-67 positivity of 50% or higher, which correlates with the poor clinical outcome compared to 70.7% of DLC (p=0.014). We conclude that subdivision of the diffuse large B-cell lymphoma category of the REAL classification is necessary in terms of prognostic significance in correlation with Ki-67 proliferative index.

Transthoracic Fine Needle Aspiration Cytology of the Lung / 대한세포병리학회지

The authors analysed 2,653 cases of transthoracic fine needle aspiration cytology of the lung to evaluate the diagnostic accuracy and its limitation. A comparison was made between the original cytologic and the final histologic diagnoses on 1,149 cases from 1,074 patients. A diagnosis of malignancy was established in 38.3% benign in 48.1%, atypical lesion in 2.3%, and inadequate one in 11.9% of the cases. Statistical data on cytologic diagnoses were as follows; specificity 98.9%: sensitivity of procedure, 76.8%: sensitivity of diagnosis, 95.5%: false positive 5 cases: false negative 18 cases: predictive value for malignancy, 98.8%: predictive value for benign lesion, 79.5%: overall diagnostic efficiency, 87.5%: typing accuracy in malignant tumor, 80%.

An Autopsied Case of Primary Pulmonary Hypertension

A twenty four-year-old female patient had suffered progressive dyspnea for 6 years until death. She denied any symptoms suggestive of connective tissue disease, or deep vein thrombosis. She suffered an episode of pontine infarct in 1995. Four years after diagnosis of primary pulmonary hypertension, she died of sudden death during hospitalization. Gross features of pulmonary arteries at autopsy were as follows: left main pulmonary artery showed dilation of the lumen and thickening of the wall, and right main pulmonary artery was markedly dilated and contained fresh thrombus. Hematoxylin and eosin-stained sections of lung tissue showed plexiform lesions of pulmonary arteries, complete luminal obliteration of pulmonary arterioles and dilated lesion of pulmonary arterioles, and capillaries. This patient represents a typical case with a primary pulmonary arteriopathy with plexiform lesions with thrombotic lesion, demonstrating the importance of thrombosis in situ in the pathogenesis of primary pulmonary hypertension. To our knowledge, this is the first autopsy report on the primary pulmonary hypertension in Korea.

A Study of Auditory Brainstem Responses in Neonates with Hyperbilirubinemia and Their Neurodevelopmental Outcome

Neonatal hyperbilirubinemia is a significant risk factor for the developemtn of otoneurologic disorder. Hyperbilirubinemia resulting in kernicterus produces widespread neuronal damage with the most common sites of staining and destruction involving the hippocampus, basal ganglia and the brainstem nuclei in the floor of the fourth ventricle, including the dorsal cochlear nucleus. ABR may be a useful tool for the monitoring early bilirubin toxicity and postcteric sequelae in infants. This study attempts to evaluate the clinical neurodevelopmental outcome in hyperbilirubnemic infants requiring exchange transfusion through the assessment of ABR. Eight hyperbilirubinemic neonates with severely abnormal ABR findings and twelve hyperbilirubinemic neonates with normal ABR findings were studied to assess their neurodevelopemental outcome. The results were as follows; 1) There were 8 severely abnormal ABR cases, including 5 cases of bilateral flat wave and 3 cases of unilateraly elevated hearing throeshold. 2) The major cause of hyperbilirubinemia was ABO incompatibility(65%) 3) Significant clinical finding associated with severely abnormal ABR was kernicterus(p<0.05) 4) Significant laboratory findings associated with severely abnormal ABR were lower levels of hemoglobin and hematocrit(p<0.05) 5) 2 cases of bilateraly flat ABR and 3 cases of unilaterally elevated hearing threshold could be classified into sensorineural type hearing defect by latency-intensity function curve. 6) At the follow up tests of 3 cases of bilaterally flat ABR, 2 cases showed no change and 1 case showed mild improvement. 7) Among 5 follow up cases of severely abnormal BR, only 1 case showed normal neurodevelopmental outcome, 3 cases showed major neurodevelopmental defect and 1 case showed minor neurodeveoplemental defect. Among them, 1 case has had definite hearing disability.

A Study of Auditory Brainstem Responses in Neonates with Hyperbilirubinemia and Their Neurodevelopmental Outcome

Neonatal hyperbilirubinemia is a significant risk factor for the developemtn of otoneurologic disorder. Hyperbilirubinemia resulting in kernicterus produces widespread neuronal damage with the most common sites of staining and destruction involving the hippocampus, basal ganglia and the brainstem nuclei in the floor of the fourth ventricle, including the dorsal cochlear nucleus. ABR may be a useful tool for the monitoring early bilirubin toxicity and postcteric sequelae in infants. This study attempts to evaluate the clinical neurodevelopmental outcome in hyperbilirubnemic infants requiring exchange transfusion through the assessment of ABR. Eight hyperbilirubinemic neonates with severely abnormal ABR findings and twelve hyperbilirubinemic neonates with normal ABR findings were studied to assess their neurodevelopemental outcome. The results were as follows; 1) There were 8 severely abnormal ABR cases, including 5 cases of bilateral flat wave and 3 cases of unilateraly elevated hearing throeshold. 2) The major cause of hyperbilirubinemia was ABO incompatibility(65%) 3) Significant clinical finding associated with severely abnormal ABR was kernicterus(p<0.05) 4) Significant laboratory findings associated with severely abnormal ABR were lower levels of hemoglobin and hematocrit(p<0.05) 5) 2 cases of bilateraly flat ABR and 3 cases of unilaterally elevated hearing threshold could be classified into sensorineural type hearing defect by latency-intensity function curve. 6) At the follow up tests of 3 cases of bilaterally flat ABR, 2 cases showed no change and 1 case showed mild improvement. 7) Among 5 follow up cases of severely abnormal BR, only 1 case showed normal neurodevelopmental outcome, 3 cases showed major neurodevelopmental defect and 1 case showed minor neurodeveoplemental defect. Among them, 1 case has had definite hearing disability.

A case of cerebro-oculo-facio-skeletal syndrome

No abstract available.

Clinical and statistical observation for very low birth weight infants

No abstract available.