Diffuse large B-cell lymphoma with continuously elevated immunoglobulin M following treatment: a case report with pathologic, immunophenotypic, and molecular analyses.

A rare subtype of diffuse large B-cell lymphoma (DLBCL) has been reported to be accompanied by elevated immunoglobulin M (IgM) paraprotein in the serum at diagnosis, called as IgMs-DLBCL. The monoclonal IgM paraprotein disappears soon after treatment in most of these patients. Here, we described a DLBCL patient with continuously elevated IgM following therapy. A 59-year-old male was diagnosed with DLBCL (GCB subtype per Hans algorithm, stage IA) with involvement of the right cervical lymph node. After six cycles of immuno-chemotherapy with the R-CHOP regimen, complete metabolic remission was achieved, but an elevated level of serum IgM persisted. To investigate the origin of elevated IgM, pathologic, immunophenotypic, and molecular analyses of lymph node and bone marrow (BM) samples were performed pre- and post-treatment. BM infiltration of lymphoplasmacytic cells, and a typical immunophenotypic profile by flow cytometry supported the diagnosis of Waldenström macroglobulinemia (WM). The MCD subtype of DLBCL was identified by next-generation sequencing of the lymph node at initial diagnosis characterized by co-occurring point mutations in MYD88 L265P and CD79B. Additionally, two different dominant clonotypes of the immunoglobulin heavy chain (IGH) were detected in the lymph node and BM by IGH sequencing, which was IGHV 3-11*06/IGHJ 3*02 and IGHV 3-11*06/IGHJ 6*02, respectively, speculating to be two independent clonal origins. This study will provide a panoramic understanding of the origin or biological characteristics of DLBCL co-occurring with WM.

Aberrant Expression of miR-142-3p and its Target Gene HMGA1 and FZD7 in Breast Cancer and its Clinical Significance.

BACKGROUND: Breast cancer is the second leading cause of cancer-related death among women worldwide. The aim of this study is to investigate the role of miR-142-3p in breast cancer cells and the related mechanism. METHODS: Sixty paired breast cancer tissues were collected and 60 breast tissues from patients with mammary hyperplasia served as the control group. The expression of miR-142-3p was examined using RT-qPCR methods; moreover, we also performed receiver operating characteristic (ROC) curve analysis to determine whether miR142-3p can distinguish breast cancer patients from the controls. Next, HMGA1 and FZD7 have been predicted as target genes of miR-142-3p, and the expressions of HMGA1 and FZD7 in breast cancer tissue and the control group were examined using RT-qPCR and western blot methods. RESULTS: miR-142-3p was significantly down-regulated in breast cancer tissue compared with the controls, and the levels of miR-142-3p was negatively correlated with the tumor size, degree of differentiation, and metastasis (p < 0.01). Moreover, results of ROC curve analysis indicated that the expression of miR-142-3p can distinguish between patients with breast cancer and the control group (AUC = 0.819, 95% CI, 0.756 - 0.881). Furthermore, the expressions of HMGA1 and FZD7 were significantly up-regulated in patients with breast cancer compared with the controls. The level of miR-142-3p was negatively correlated with expressions of HMGA1 (r = -0.3507, p = 0.006) and FZD7 (r = -0.3410, p = 0.0077) in patients with breast cancer. CONCLUSIONS: Our results proved that miR-142-3p may serve as a tumor suppressor in breast cancer by suppressing the expression of oncogene HMGA1 and FZD7, suggesting that miR-142-3p has the potential to become a diagnostic marker and therapeutic target for the early diagnosis and treatment of breast cancer.

Clinicopathologic and Immunophenotypic Features of Primary Intestinal Extranodal NK/T-Cell Lymphoma, Nasal Type.

Primary intestinal extranodal NK/T-cell lymphoma, nasal type, is an extremely rare type of lymphoma with poor prognosis, and early diagnosis is challenging. Here we have investigated the clinicopathologic features and immunophenotypes of primary intestinal extranodal NK/T cell lymphomas, nasal type, in 10 Chinese patients. Complete staging data showed that 1 patient had stage I disease, 7 had stage II disease, and 2 had stage III disease. Eight of 10 (80%) patients had lymphadenopathy and none had bone marrow involvement. All the patients had a low International Prognostic Index (IPI) score (<3) at presentation. The median age at the time of diagnosis was 37.5 years (range = 24-68 years). All the patients died within 21 months, and the median survival time was 9.5 months (range = 2-21 months). So the conventional IPI and staging system failed to predict the outcome of the patients with the lymphoma. Except for the size of tumor cells, most of the morphologic features of the cases we studied were similar to those involving the midline facial tissue. Immunohistochemical studies showed the expression of cytotoxic markers (100%), CD2 (100%), CD3ε (90%), CD56 (80%), P53 (60%), CD30 (30%), LMP1 (30%), EBNA3A (0%). Nine cases (90%) highly expressed Ki-67. In situ hybridization for Epstein-Barr virus-encoded small RNA was positive in all cases.

Primary extranodal NK/T cell lymphoma, nasal-type of uterus with adenomyosis: a case report.

Natural killer (NK)/T cell lymphoma of the female genital tract is extremely rare. We here report a case of 'nasal type' NK/T cell lymphoma arising in the uterus with adenomyosis in a 41-year-old woman with fever and hypogastralgia. The histologic analysis demonstrated a highly aggressive tumor with characteristic angiocentric/angiodestructive growth pattern and focal necrosis. The lymphoma cells displayed a CD3ϵ/CD56/TIA-1/granzyme-B/Perforin-positive and CD20/CD79a/CD4/CD8-negative immunophenotype and positive for Epstein-Barr virus by EBER in situ hybridization. Clinically, the disease was limited to the uterus at the initial diagnosis, but progressed rapidly. The patient died on day 54 after hysterectomy, irrespective of intensive chemotherapy. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1323474831125945.

[SHP-1 gene's methylation status of Daudi lymphoma cell and the demethylation effect of 5-aza-2'-deoxycytidine].

OBJECTIVE: To explore the transcription regulation of 5-aza-2'-deoxycytidine(5-Aza-CdR) on SHP-1 gene and its effects on Daudi cell line growth. METHODS: MTT method and flow cytometry were used to detect the growth and apoptosis of Daudi cells after treated with different dosage of 5-Aza-CdIR. Bisulfite sequencing PCR ( BSP) , T-A cloning and sequence analysis were evaluated for methylation status. The SHP-I mRNA and protein were determined by reverse transcription polymerase chain reaction (RT-PCR) ,immunohistochemistry. RESULTS: (1)After 7 d treatment with 2. 00 micromol/L of 5-Aza-CdR, all cytosines (C) in Daudi cells genome DNA were converted to thymidine, and SHP-1 mRNA and protein expressed again in the cells while those Cs in CpG dinucleotides in untreated Daudi cells remained Cs; (2)5-Aza-CdR inhibited the cell growth,The effects within certain extent were dose and time dependent:after 72 h treatment with 5-Aza-CdR at 200. 00, 20. 00, 2. 00 and 0. 20 micromol/L, the inhibitive rates were 72. 0% , 65. 1%, 51. 5%, 28.8% ,23.4% respectively; (3) 5-Aza-CdR increased apoptosis rate of tumor cells with a dose and times dependent manner within certain extent, too:at the 1,3,5 d treatment with 5-Aza-CdR 2. 00 micromol/L,the apoptosis rates were 2. 3% ,10. 8 % and 17. 1% ; respectively. (4) 5-Aza-CdR also changed cell cycle of tumor cells: at 24 h treatment with 5-Aza-CdR 2.00 micromol/L,92. 7% tumor cells stopped at S phase and G, phase cells were increased gradually with time. CONCLUSION: DNA promoter hypermethylation is associated with SHP-1 gene silence in Daudi lymphoma cell line. 5-Aza-CdR could effectively cause demethylation and inhibit the growth of tumor cell by reactivating the gene transcription.

[Clinical and pathological reassessment of 493 cases of non-Hodgkin's lymphomas according to current WHO classification of lymphoid neoplasms].

OBJECTIVE: To investigate the clinical and pathological features of non-Hodgkin's lymphoma (NHL) and to evaluate the applicability of the new WHO classification of lymphoid neoplasms. METHODS: According to the new WHO classification, a total of 500 cases of non-Hodgkin's lymphoma diagnosed during the period 1992 - 2003 were reviewed and reappraised with their morphological, immunological and clinical characteristics. Clinical survival analysis was performed in 156 cases that accompanied with follow-up data. RESULTS: Among 500 cases previously diagnosed as lymphomas, 493 cases (98.6%) were confirmed to be NHL, of which B-cell neoplasms was 69.0% and T/NK-cell neoplasms 29.8%. Overall, 6 subtypes including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), unspecified peripheral T-cell lymphoma (PT-un), precursor T-lymphoblastic lymphoma (T-LBL), extranodal marginal zone B-cell lymphoma of MALT type (MALT) and B-small lymphocytic lymphoma (B-SLL) were among the most common subtypes. In pediatric and young patient populations, the most common subtypes were LBL, DLBCL and Burkitt's lymphoma. The frequency of LBL in all patients, especially in the juniors, was much higher than those reported outside Mainland China, and the frequency of FL was much higher than the reported in Mainland China. The frequency of FL was much higher than the reported in Mainland China. Clinical survivals among different histological subtypes of NHL varied considerably with statistic significance (P < 0.001). Marginal zone B-cell lymphoma and SLL demonstrated the best prognosis, LBL and PT-un both the worst, whereas DLBCL and FL had an intermediate prognosis, however, subgrouping of FL according to WHO classification did not reveal a significant survival difference (P > 0.05). CONCLUSIONS: Basing upon the results of a comprehensive survey on the morphologic features, immunophenotyping and clinical data of the above cases, the new WHO classification of lymphoid neoplasms is practical and easily applicable for routine pathological evaluation of lymphoproliferaive disorders and in guiding the clinical management. It appears that the diagnostic and grading criteria for FL in Mainland China need to be re-evaluated.