Complete Remission and Long-term Survival of a Patient with a Diffuse Large B-cell Lymphoma Under Viscum album Extracts After Resistance to R-CHOP: A Case Report.

BACKGROUND: A nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) is a lymphoproliferative neoplasm with a fair prognosis, but the possibility of a malignant transformation into a diffuse large B-cell lymphoma (DLBCL) is high. DLBCL progresses aggressively. Introduction of rituximab into therapy had led to improved outcomes. The use of Viscum album extracts (VAE) in cancer is established, but their application in lymphoma are rare. CASE PRESENTATION: A 65-year-old patient was diagnosed with DLBCL stage IIa with splenomegaly, transformed from a NLPHL, after a 30-year history of repeatedly enlarged inguinal lymph nodes. The patient initially rejected chemotherapy. After his tumor pain increased, he accepted the consecutive therapies bendamustine plus vincristine plus prednisolone, trofosfamide, and rituximab plus cyclophosphamide plus hydroxydaunorubicin plus vincristine plus prednisone (R-CHOP), inducing only a slight regression of the splenic lesions. VAE was additionally applied to R-CHOP. Five months after termination of chemotherapy - under continued VAE therapy in increasing dosage- regression of paraaortal lesions was found. The patient fully recovered under continuous VAE application and is in ongoing complete remission and in a good state of health 17 years after the initial diagnosis. CONCLUSION: As complete remission of lymphoproliferative disorders after VAE treatment has been previously reported, further investigations of VAE in lymphoma seem highly worthwhile.

Intralymphatic Spread is a Rare Finding Associated With Poor Prognosis in Diffuse Large B-Cell Lymphoma With Extranodal Involvements.

Intralymphatic spread is common in solid cancers, but has been rarely studied in lymphomas. Review of 635 extranodal specimens from 475 diffuse large B-cell lymphoma (DLBCL) patients revealed intralymphatic spread in 10 surgical resection specimens from 10 patients including 9 de novo DLBCLs and 1 Richter transformation. The prevalence in de novo DLBCL with extranodal involvements was 1.65%. The most common involved site of intralymphatic spread was the gastrointestinal tract, followed by the female genital tract and breasts. Lymphatic vessels, lined by D2-40-positive endothelial cells, were expanded by lymphoma cells, reminiscent of intravascular lymphoma or tumor emboli. None of the involved lymphatic vessels were located in the mucosa. Patients with intralymphatic spread had a trend of lower overall response rate and a trend of higher progressive disease than those without intralymphatic spread. Compared with patients without intralymphatic spread, those patients with intralymphatic spread had a shorter median overall survival (14.3 vs. 96.2 mo; P=0.004) and a shorter median progression-free survival (11.2 vs. 64.2 mo; P=0.01), respectively. Multivariate analyses showed that intralymphatic spread was an independent poor prognostic factor for overall survival (hazard ratio, 3.029; 95% confidence interval, 1.315-6.978; P=0.009), irrespective of the National Comprehensive Cancer Network-International Prognostic Index, B symptoms, and serum albumin levels. Among patients who underwent surgical resection, intralymphatic spread was still an independent prognostic factor. In conclusion, our study demonstrated extranodal intralymphatic spread in DLBCL. Inspiringly, this rare morphologic finding may serve as a new negative prognostic indicator in DLBCL with extranodal involvements.

[Primary central nervous system diffuse large B cell lymphoma: a clinicopathologic and molecular study].

Objective: To investigate clinicopathologic characteristics, immunophenotype and EB virus-related molecular genetic alterations in primary central nervous system diffuse large B cell lymphoma (DLBCL) along with correlation with clinical prognosis. Methods: A total of 30 cases of primary central nervous system DLBCL were retrospectively studied by retrieving clinical data, histological evaluation and immunophenotyping by EnVision two steps methods. The expression of EBER mRNA was detected by in situ hybridization and bcl-2, bcl-6 and C-MYC gene abnormalities were analyzed by interphase fluorescence in situ hybridization. Results: The cases included 18 males and 12 females (sex ratio of 1.5∶1.0) with an age ranging from 24 to 78 years (average age of 52 years, the median age of 53 years). The single primary clinical presentation was focal neurologic deficits. Tumor locations were supratentorial (21 cases), subtentorial (7 cases), involving both locations in 2 cases. Diffuse growth pattern was observed with large lymphoid cells mostly resembling centroblasts with abundant basophilic cytoplasm with oval to round, vesicular nuclei containing fine chromatin. An angiocentric and angiodestructive growth pattern was also present. Other features included perivascular space invasion. Immunohistochemical staining using a panel of CD10, bcl-6 and MUM1, six cases were germinal center-like (GCB) and 24 cases were non-germinal central-like (non-GCB). The positive rates of bcl-2, bcl-6 and C-MYC were 53.3% (16/30), 80.0% (24/30) and 20.0% (6/30), respectively. Genetic alterations were detected by FISH and the gene arrangement rates of bcl-2, bcl-6 and C-MYC were 3.3% (1/30), 16.7% (5/30) and 3.3% (1/30), respectively. There were 19 cases in stage 0-1 disease and 11 cases had stage 2-3 disease. Postoperative follow-up for average 13.6 months showed the median survival of 10 months, one-year survival of 46.7% and 16 patients died within a year. Conclusions: The clinical prognosis of primary central nerve system DLBCL depends on age, clinical performence status score, IPI score, immune classification and treatment. Patients typically progress rapidly with the high mortality within one year of diagnosis. Surgical resection combined with high-dose methotrexate or cytarabine chemotherapy offer the best treatment option.

Prognostic impact of germinal center-associated proteins and chromosomal breakpoints in poor-risk diffuse large B-cell lymphoma.

PURPOSE: Outcome of diffuse large B-cell lymphoma (DLBCL) with a germinal center B-cell (GCB) expression profile is superior to that of non-GCB DLBCL. This conclusion is mainly derived from patients with mixed international prognostic index (IPI) risk profiles treated with CHOP-like therapy (cyclophosphamide, doxorubicin, vincristine, and prednisone). We wondered whether the prognostic impact of the expression profile would hold out in a homogeneous cohort of poor-risk DLBCL patients treated with high-dose sequential therapy (HDT) and autologous stem-cell transplantation (ASCT) as first-line therapy. PATIENTS AND METHODS: DLBCL from 66 newly diagnosed poor-risk patients, treated in two sequential prospective Dutch Hemato-Oncology Association (HOVON) trials, were studied retrospectively for expression of CD10, bcl6, MUM1/IRF4, bcl2, Ki67, and CD21+ follicular dendritic cells (FDC) by immunohistochemistry, and for the breakpoints of BCL2, BCL6, and MYC by fluorescent in situ hybridization (FISH). Lymphomas with any follicular component were excluded. RESULTS: A GCB immunophenotype profile was found in 58% and non-GCB immunophenotype profile in 42% of the tumors. Clinical characteristics of both groups were similar. Complete response (CR) rate was higher in patients with CD10+ tumors (58% v 30%; P = .03). A GCB immunophenotype profile, its constituting markers CD10 more than 30% and MUM1 less than 70%, and bcl2 less than 10% were each associated with a better overall survival (OS). FDC networks, equally present in GCB and non-GCB tumors, had superior CR (73% v 31%; P = .01), but disease-free survival rates were lower and there was no difference in OS rates. None of the breakpoints had a prognostic impact on outcome. CONCLUSION: Also in patients with poor-risk DLBCL treated with HDT and ASCT, the GCB immunophenotype and bcl2 expression retained a major impact on survival.

[Primary large B-cell lymphoma of the thyroid. Apropos of 2 cases]. / Linfoma primitivo della tiroide a larghe cellule B. A proposito di due casi.

Two cases of primary large B-cell non-Hodgkin's lymphoma are described. Both cases had typical symptoms: a sudden growth of thyroid in these female patients at their sixth decade of life. The differential diagnosis between undifferentiated carcinoma and lymphoma of the thyroid, uncertain with clinical and ultrasound examination, was defined by a fine needle biopsy (FNAB). Patients underwent a radical resection which permitted a correct cancer staging even in the presence of laterocervical lymph nodes swelling. Histological examination of the surgical specimen confirmed the presence of a large B-cell non-Hodgkin's lymphoma while the immunophenotypical analysis detected the expression of the common leukocytic antigen and B-correlated antigens CD20, CD74, CDW75 and CD79A. In both cases chemotherapy and radiotherapy were carried out.