- Diagnostic Utility of Polymerase Chain Reaction-Based Clonality Analysis for Immunoglobulin Heavy Chain Gene and T-cell Receptor Gamma Chain Gene Rearrangement in Lymphoid Neoplasms.
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Eun Yoon Cho, Young Hyeh Ko, Dae Shick Kim, Jae Joon Han, Howe J Ree
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Korean J Pathol. 2001;35(6):461-469.
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 Abstract
- BACKGROUND
The clonality of lymphoid infiltrates determined by polymerase chain reaction (PCR) for immunoglobulin heavy chain (IgH) or T cell receptor (TCR) genes is not only useful in confirming the diagnosis of malignant lymphoma but also in establishing the lineage of a clonal lymphoid proliferation. We analyzed the efficiency of PCR analyses for IgH and TCRgenes that have been routinely applied for the diagnosis of malignant lymphoma in our laboratory.
METHODS
Paraffin sections of 200 cases were analyzed by seminested PCR. Primers were FRIIIA-LJH/VLJH consensus primer for IgH gene and V-J consensus primer for TCR gene.
The cases showing negative results by PCR for TCR gene were further analyzed by multiplex V family primers with heteroduplex analysis.
RESULTS
PCR approach for IgH gene allowed detection of clonality in 100% of cases with false positive rate of 0.3% and false negative rate of 0%. The combination of PCR for TCR consensus primers with multiplex V family primers allowed detection of clonality in 91% of cases with false positive rate of 0.6% and false negative rate of 10.3%.
CONCLUSIONS
Combined analysis of IgH and TCR gene rearragnements by the PCR technique followed by heteroduplex analysis can be a useful diagnostic adjunct to determine the clonality of various lymphoproliferative diseases with high sensitivity. But clinical, morphological and immunophenotypical correlation should be considered to reach the final diagnosis due to a few false positive cases.
- Primary Nodal Marginal Zone B-cell Lymphoma: Clincopathologic Analysis of Splenic and Mucosa-Associated Lymphoid Tissue Type.
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Jae Joon Han, Young Hyeh Ko, Eun Yoon Cho, Mi Kyung Kim, Nam Hun Kim, Howe J Ree
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Korean J Pathol. 2001;35(6):470-476.
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Abstract
- BACKGROUND
Primary nodal marginal zone B-cell lymphoma (MZBL) is recently divided into mucosa-associated lymphoid tissue (MALT) type and splenic type. Herein, we analyzed clinicopathologic differences of those two types of nodal MZBL.
METHODS
Histologic and clinical findings of eleven cases of primary nodal MZBL lymphoma were reviewed.
Immunohistochemical stains for IgD, Ki-67, CD3, and CD20 were performed.
RESULTS
The cases were classified as splenic type in four, MALT type in five, and unclassified in two. The age at presentation was 36.7 years old (range: 16-73) in splenic type and 48 years old (range: 31-68) in MALT type. Two patients with splenic type and one with MALT type had a long history of lymphadenopathy up to 9 years. Whereas tumors of splenic type showed nodular infiltration of tumor cells with follicular colonization and hyperplastic germinal center, tumors of MALT type showed mainly sinusoidal or parafollicular infiltration and atrophic germinal centers.
All the patients with splenic type were alive at last follow-up and one patient with MALT type died of disease at 5 months after diagnosis.
CONCLUSIONS
Although the number of cases we analyzed was small, splenic type seems to be distinct from MALT type and lower grade neoplasm.
- Histopathologic Features and Immunophenotype of 19 Primary Cutaneous Lymphomas.
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Hee Sung Kim, Young Hyeh Ko, Howe J Ree
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Korean J Pathol. 1999;33(12):1111-1119.
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Abstract
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- The diagnosis of primary cutaneous lymphoma is based on a combination of clinical, histological, immunophenotypic and genetic criteria.
Nineteen cases of primary cutaneous lymphomas were studied for clinicopathologic, immunophenotypic, and genetic features.
Seventeen (89%) cases were T cell origin and two cases (11%) were B cell origin.
CD30-positive cutaneous lymphoproliferative disorder was the most frequent subtype, occupying 42% (8 cases) of the cases. CD8 was positive in 5 cases consisting of 3 cutaneous T cell lymphomas and 2 anaplastic large cell lymphomas. CD4 was positive in 2 cases of mycosis fungoides and 3 cases of lymphomatoid papulosis. Six (67%) of 9 cases of cutaneous T cell lymphoma were positive for TIA-1.
Ten (83%) out of 12 cases showed clonal rearrangements of TCR gamma genes, however, one T/NK cell lymphoma and one anaplastic large cell lymphoma did not. EBV association was detected only in T/NK cell lymphomas among 10 cases examined. In conclusion, our study showed higher proportion of CD30-positive lymphoproliferative disorders and less frequent mycosis fungoides in Korea compared to the incidences in Western countries.
Our immunostaining results suggested that mycosis fungoides and lymphomatoid papulosis are CD4-positive T cell origin, however, the remaining primary cutaneous T cell lymphoma is predominantly CD8-positive cytotoxic T cell origin.
- Analyses of Genetic Alterations in Breast Cancers by Comparative Genomic Hybridization.
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Jin Man Kim, Young Mi Jeon, Young Hyeh Ko, Kyu Sang Song, Howe J Ree, Joo Seob Keum, Jae Hyuk Lee, Sun Hoe Koo
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Korean J Pathol. 1999;33(8):603-613.
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Abstract
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- Transformation and progression of breast cancer are thought to be caused by an accumulation of complex genetic alterations, but little is known about specific changes.
In this study, the author has undertaken a genome-wide screening to detect genetic changes in 20 cases of breast cancer among Koreans, including 16 infiltrating ductal carcinomas, 2 medullary carcinomas, 1 invasive lobular carcinoma, and 1 borderline phyllodes tumor. Comparative genomic hybridization (CGH) was used to screen for DNA sequence gains and losses across all human chromosomes.
Simultaneous immunohistochemical staining for c-erbB-2 (Her-2/neu), c-myc, cyclin D1, and p53 protein was done to make comparisons with nuclear grade and that with CGH results.
Biotin-labeled tumor DNA and digoxigenin-labeled normal DNA were hybridized to normal metaphase cells. The fluorescence signals were captured by fluorescence microscope after detection by avidin-FITC and anti-digoxigenin rhodamine. Then, the ratio of fluorescence was calculated by an image analyzer.
The immunohistochemical staining was done in paraffin-embedded tissue with an LSAB kit and avidin-biotin complex (ABC) method. The CGH results showed gains on chromosomes 8q (40%), 1q (30%), 17q (15%), 20q (15%), 18q (15%), 5p (15%), and 13q (15%). Deletions were on chromosomes 17p (45%) and 22q (20%). High-level amplifications (green/red ratio >1.5) were noted on chromosomes 1p31, 1q, 3q25-qter, 5p, 7q31-qter, 8q, 9p22-qter, 10p, 11p, 11q22-qter, 12p, 12q24, 14q21-qter, 15q23-qter, 17q, 18p, 18q12-qter, 20p, and 20q. By comparison with infiltrating ductal carcinoma, the two medullary carcinomas showed high-level amplification on chromosomes 1p31, 1q, 8q, 10p, 11p and 12p. c-erbB-2, c-myc, cyclin D1, and p53 protein expression was immunohistochemically detected in 9 of 20 (45%), 8 of 20 (40%), 10 of 20 (50%), and 13 of 20 (65%), respectively. The results indicate that the amplification on chromosome 8q, 1q and the deletions on chromosomes 17p and 22q are the most frequent genetic alterations in breast cancers among Koreans. The results reveal a different pattern of genetic alteration from previous studies. The CGH results were not correlated with the immunohistochemical profiles. The amplification pattern of medullary carcinomas was quite different from the pattern of infiltrating ductal carcinomas. The CGH was thought to be very useful in the screening of genetic alterations of solid tumors.
- Diagnostic Usefulness and Limitation of Fine Needle Aspiration Cytology of Lymph Node: Analysis of 176 Cases Confirmed by Biopsy .
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Hee Sung Kim, Dae Soo Kim, Young Lyun Oh, Young Hyeh Ko, Howe J Ree
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Korean J Cytopathol. 1999;10(1):35-42.
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Abstract
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- The accuracy of fine needle aspiration cytology(FNAC) of the lymph node was investigated through a review of 176 FNAC cases and the corresponding biopsies. We chose 157 FNAC cases after the exclusion of 19 inadequate ones. Sensitivity of malignancy was 94.0%, specificity 100%, false negativity 6.0%, and false positivity 0.0%. The overall diagnostic accuracy was 96.8%. Sensitivity of metastatic carcinoma was 98.0% and that of malignant lymphoma was 87.9%. False negative cases included one metastatic carcinoma and four malignant lymphomas. The aspirates of metastatic carcinoma with false negativity exhibited a diffuse smear of keratin debris without viable cells, which led to the difficulty in differentiation from benign epithelial cyst. The cases of malignant lymphoma with false negative diagnosis were two Hodgkin diseases, one Lennert's lymphoma, and one peripheral T cell lymphoma in the histologic sections. On the analysis of 39 cases of tuberculosis, 17 cases(43.6%) were diagnosed as tuberculosis, 4(10.3%) as granulomatous lymphadenitis, 3(7.7%) as necrotizing lymphadenitis, and 15(38.5%) as reactive hyperplasia or pyogenic inflammation. Sensitivity of tuberculosis was 53.9%. In conclusion, lymph node FNAC is an excellent non-invasive diagnostic tool for the diagnosis of metastatic carcinoma. The diagnostic accuracy of malignant lymphoma could be improved with flow cytometry or polymerase chain reaction for antigen receptor genes. For the FNAC diagnosis of tuberculosis, AFB stain, culture, and PCR would be helpful as adjuvant techniques.
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