A case of MALT lymphoma of the urinary bladder / 대한내과학회지

Primary lymphoma of the urinary bladder is a rare non-epithelial bladder tumor accounting for less than 1% of all bladder tumors. Approximately 17 cases of MALT lymphomas of bladder have been reported in the literature. Most reported MALT lymphomas of bladder have a female sexual preponderance with a mean age of 58 years with common presenting symptoms of hematuria, dysuria and urinary frequency. The reported prognosis of MALT lymphoma of the urinary bladder is excellent. We report a case of MALT lymphoma of urinary bladder in a 57-year-old woman patient who presented with a two-year history of persistent dysuria and urinary frequency. An intravenous pyelogram and cystoscopy revealed a 1 cm focal elevated lesion at the base of urinary bladder. The tissue obtained by transurethral resection (TUR) showed plasma cell infiltration consistent with low grade marginal zone B cell lymphoma. The immunohistochemical studies showed an immunoglobulin restriction to lambda light chain while the nested polymerase chain reaction analysis of the tissue showed a monoclonal Ig heavy-chain gene rearrangement. The clinical staging protocol revealed that the tumor was primarily arising from the urinary bladder with no evidence of other site involvements. The patient received radiation therapy of 3060 cGy in 17 fractions.

Mantle Cell Lymphoma/Leukemia in Bone Marrow: Lacking Evidence of t(11;14) / 대한임상병리학회지

BACKGROUND: Mantle cell lymphoma/leukemia (MCL) is a distinctive disease entity that has been characterized by specific histopathologic, immunologic, and cytogenetic features. The characteristic cytogenetic abnormality of MCL is t(11;14)(q13;q32), that results in cyclin D1 overexpression. We have experienced 12 MCL cases with bone marrow involvement that were lacking evidence of t(11;14). We tried to review the cases. METHODS: We reviewed the bone marrow findings, immunophenotypic, cytogenetic studies including fluorescent in situ hybridization (FISH) analysis using IGH/CCND1 probes and medical records of 12 patients that were diagnosed with MCL based on immunophenotypic results during the period 1997 to 2001. RESULTS: The patients had a median age of 63 (50-70) years with male-to-female ratio of 3:1. All patients showed hepatosplenomegaly with varying degrees of peripheral blood involvement (2-93%), and lymphocytosis was found in 7 cases. Other presenting features were palpable lymph nodes (83%) and B symptoms (25%). The malignant cells were quite heterogenous in morphology from centrocytic to blastic variants. Most cases showed typical immunophenotypes-expression of CD19, bright CD20, FMC7, CD5 and bright-light chains with negative CD23. Immunohistochemical staining with cyclin D1 on marrow biopsies showed mostly negative results. Among the eleven cases in which cytogenetic studies were possible, four cases showed complex karyotypes, and three that involved 14q32. Strikingly, no one showed t(11;14) in G-banding analysis and only 2 cases showed IGH/CCND1 rearrangement by FISH. CONCLUSTIONS: Most MCL cases with typical immunophenotypic findings did not show evidence of specific cytogenetic features. Although further workups for molecular pathogenesis and clinical follow-up of the above cases need to be done, we suggest a new disease entity, t(11;14)-negative MCL.

Clinical investigation of gastric MALT lymphoma / 대한내과학회지

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach has recently been defined as a distinct clinicopathologic entity, often associated with Helicobacter pylori (H. pylori) infection. Characteristics and treatment outcomes of 57 patients with gastric MALT lymphoma were analyzed. METHODS: Retrospective analysis of 57 cases of gastric MALT lymphoma who underwent treatment with various modalities at Samsung Medical Center from Mar. 1995 to Jul. 2000 was performed. RESULTS: The median age of the patients was 47 years (ranged from 22 to 75 years) and the ratio of males to females was 1.1:1. The presenting symptoms were abdominal pain, indigestion and GI bleeding. By Modified Ann Arbor system, stage IE accounted for 70.2%, stage II1E 14.0%, stage II2E 14.0%, and stage IV 1.8%, respectively. H. pylori had been evaluated histologically in 49 cases of which 81.6% was positive. Low grade histology accounted for 71.9% and high grade histology 28.1%. Treatment modalities included H. pylori eradication, surgery, chemotherapy, radiotherapy and their combination therapy. In one case, the patient was observed without treatment. Complete remission rate was 98.2%. H. pylori eradication alone resulted in lymphoma regression successfully in 20 out of 23 patients. With median follow-up of 33 months (3-61 months), median survival was not reached. Overall 3 year survival rate was 94.7%. CONCLUSION: Regardless of treatment modality, high survival rate (3 year survival rate 94.7%) was obtained. H. pylori eradication was feasible and safe in the cases of low grade, stage I, and H. pylori-positive lymphoma, and allowed stomach preservation. Longer follow-up evaluation is required to determine the long-term efficacy and side effects of H. pylori eradication.

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

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

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.

Extra-gastric MALT lymphoma: Analysis of 50 cases / 대한내과학회지

BACKGROUND: Mucosa-associated lymphoid tissue(MALT) lymphoma has an indolent natural course. However, extra-gastric MALT lymphoma has been reported to have more frequent relapses and shorter time to progress than gastric MALT lymphoma. We performed this study to analyze clinical features of extra-gastric MALT lymphoma. METHODS: We retrospectively reviewed the medical records of the patients who were diagnosed as extra-gastric MALT lymphoma at the Samsung Medical Center from March 1995 to January 1999. The survival was analyzed by Kaplan-Meier method. RESULTS: During the study period, extra-gastric MALT lymphoma was diagnosed in 50 patients. The median age was 51(28-87)yaers. The male to female ratio was 22:28. Commonly involved sites were conjunctiva (25/50, 50%), lung (6/50, 12%) and intestine(6/50, 12%). Histopathologically, low to high grade ratio of extra-gastric MALT lymphoma was 47:3. Among 41 patients who were staged, 32 patients(78%) had stage I or II and 9 patients(22%)had stage IV. B symptoms were seen in only 3 patients. Bone marrow involvement was observed in 4 patients. The duration of median follow up was 22 months. The 1-year and 2-year survival rates were 95.1% and 91.4% retrospectively. CONCLUSION: Majoity of our cases with extra-gastric MALT lymphoma had low grade, early stage, good treatement reponse and good prognosis.

A case report of primary T-cell lymphoma of the liver

The patient was a 50-year-old woman who presented intermittent mild fever with elevated liver enzymes for 12 years. The liver biopsy showed diffuse portal and sinusoidal involvement of lymphoid cells with minimal atypia and epithelioid histiocytic granuloma formation. Subsequent bone marrow biopsy showed lymphomatous involvement. The lymphocytes infiltrating the liver were reactive for T-cell marker and showed TCR gamma gene rearrangement. The patient was diagnosed as primary peripheral T-cell lymphoma of the liver. Indolent clinical course and resemblance with hepatitis were considered to be a rare and unique feature of this case.

Analyses of Genetic Alterations in Breast Cancers by Comparative Genomic Hybridization

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.

Histopathologic Features and Immunophenotype of 19 Primary Cutaneous Lymphomas

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.

Diagnostic Usefulness and Limitation of Fine Needle Aspiration Cytology of Lymph Node: Analysis of 176 Cases Confirmed by Biopsy / 대한세포병리학회지

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.