scholarly journals Differentiating Benign From Malignant Bone Marrow B-Cell Lymphoid Aggregates: A Statistical Analysis of Distinguishing Features

2015 ◽  
Vol 139 (2) ◽  
pp. 233-240 ◽  
Author(s):  
Abbey Johnston ◽  
Russell K. Brynes ◽  
Kaveh Naemi ◽  
Niloufar Reisian ◽  
Deepty Bhansali ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Distribution Patterns ◽  
Cell Aggregates ◽  
Diagnostic Challenge ◽  
Specific Distribution ◽  
History Of ◽  
Characteristic Features ◽  
Distinguishing Features ◽  
Lymphoid Aggregates

Context Lymphoid aggregates are seen in a minority of bone marrow biopsy specimens, and when present, their neoplastic nature is often apparent by morphologic evaluation. However, the distinction between benign and malignant aggregates can be a diagnostic challenge when there are multiple aggregates with no documented history of lymphoma. Objective To aid in the distinction between benign and malignant B-cell lymphoid aggregates. Design Previously, we described specific distribution patterns for B and T lymphocytes within bone marrow aggregates. To statistically analyze the significance of these patterns as well as previously reported criteria, we examined 128 bone marrow specimens with benign aggregates and 78 specimens with documented malignant B-cell aggregates and calculated specific odds ratios (ORs) and 95% confidence intervals (CIs) to aid in differentiating between benign and malignant B-cell aggregates. Results Aggregates with infiltrative edges (OR, 80.54; 95% CI, 31.76–204.21), a B-cell pattern (OR, 30.08; 95% CI, 13.28–68.10), paratrabecular location (OR, 10.17; 95% CI, 3.96–26.12), size greater than 600 μm (OR, 6.83: 95% CI, 3.61–12.93), or cytologic atypia correlated with malignancy. Conclusion When taken collectively, the presence of more than 2 of these characteristic features was strongly predictive of malignancy.

scholarly journals Intravascular Lymphoma in Patient With Celiac Disease With Multi Glandular Involvement

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A938-A939
Author(s):  
Mustafa Alam ◽  
Mohamad Hosam Horani
Keyword(s):  
Celiac Disease ◽  
B Cell ◽  
Cell Lymphoma ◽  
Case Reports ◽  
B Cell Lymphoma ◽  
Diagnostic Challenge ◽  
Pituitary Microadenoma ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
History Of

Abstract Case Presentation: The patient is a 60 year old male with a past medical history of celiac disease, paroxysmal Afib, iron deficiency, and CAD who presented with lightheadedness, dizziness, and fatigue. Notable workup revealed that the patient had Afib with RVR, a TSH of 0.189, Free t4 0.51an LDH of 2726, hemoglobin of 8.7, AST of 155, ALT of 19, WBC of 4.5, and serum iron of 20. The patient’s cardizem dose was adjusted and repeat transthoracic echocardiogram was unremarkable compared to history. The patient presented again with complaints of abdominal distension, postural dizziness, occasional night sweats, and fevers. Repeat workups revealed pancytopenia, proteinuria, hypotension, and anasarca most pronounced in the lower extremity and scrotum. Ultimately, a kidney biopsy revealed an intravascular B cell non-Hodgkin lymphoma (IVBCL). Notable repeat labs include a CRP of 44 and a failed ACTH stimulation test. A brain MRI revealed a 6mm pituitary microadenoma. The patient placed on an R-CHOP regiment and is scheduled for repeat MRI to rule out pituitary involvement. Discussion: IVBCL’s are a rare form of diffuse B cell lymphoma and remain a diagnostic challenge due to the variety of involved systems including skin, CNS, and endocrine. IVBCL is also known to not produce a mass or lymphadenopathy. Celiac disease is a known risk factor for non-Hodgkin’s lymphoma. A literature search reveals a few case reports with common themes of increased LDH and inflammatory markers, anemia, and hepatic and renal dysfunction. Postural hypotension can also be a presenting symptom due to IVBCL’s ability to infiltrate neurovascular tissue to cause autonomic neuropathy. However, in this case, the patient’s history of primary adrenal insufficiency makes this unlikely. Hypothyroidism secondary to pituitary and thyroid involvement was suspected due to TSH level suppressed enough for central hypothyroidism. Repeated MRI showed resolution of Pituitary Microadenoma post Chemo therapy. Sylvain Raoul Simeni Njonnou, Bruno Couturier, Yannick Gombeir, Sylvain Verbanck, France Devuyst, Georges El Hachem, Ivan Theate, Anne-Laure Trepant, Virginie De Wilde, Frédéric-Alain Vandergheynst, “Pituitary Gland and Neurological Involvement in a Case of Hemophagocytic Syndrome Revealing an Intravascular Large B-Cell Lymphoma”, Case Reports in Hematology, vol. 2019, 6 pages, 2019. https://doi.org/10.1155/2019/9625075 Catassi C, Fabiani E, Corrao G, et al. Risk of Non-Hodgkin Lymphoma in Celiac Disease. JAMA. 2002;287(11):1413 Khan MS, McCubbin M, Nand S. Intravascular Large B-Cell Lymphoma: A Difficult Diagnostic Challenge. J Investig Med High Impact Case Rep. 2014 Mar 6;2(1):2324709614526702. Pearce C, Hope S, Butchart J. Intravascular lymphoma presenting with postural hypotension. BMJ Case Rep. Published 2018 Jan 29.

Lymphoma of the Breast

1999 ◽  
Vol 123 (12) ◽  
pp. 1208-1218 ◽  
Author(s):  
Margarita Topalovski ◽  
Domnita Crisan ◽  
Joan C. Mattson
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Gene Rearrangement ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
B Cell Lymphomas ◽  
Breast Lymphoma ◽  
Gene Rearrangement Analysis ◽  
Lymphoid Aggregates ◽  
Large B Cell

Abstract Background.—Primary lymphomas of the breast are rare, accounting for 1.7% to 2.2% of extranodal lymphomas and 0.38% to 0.7% of all non-Hodgkin lymphomas. Although secondary breast lymphomas are also rare, they represent the largest group of metastatic tumors of the breast. Objectives.—To investigate the clinicopathologic and immunophenotypic characteristics of breast lymphomas, the relative frequency of primary and secondary mammary lymphomas, and in selected cases, the role of gene rearrangement analysis in diagnosis and staging of these lymphomas. Results.—We conducted a retrospective review of 22 cases of breast lymphoma diagnosed at William Beaumont Hospital, Royal Oak, Mich, during a 30-year period (1963–1994). Eleven of the 22 cases fulfilled the criteria for primary breast lymphoma; these cases represented 0.6% of all non-Hodgkin lymphomas seen in our hospital. Of the 11 cases, 5 were diffuse large B-cell lymphomas, 2 were follicle center lymphomas, 2 were marginal zone B-cell lymphomas (mucosa-associated lymphoid tissue type), 1 was a lymphoplasmacytoid lymphoma, and 1 was a peripheral B-cell neoplasm, unclassified. Using a panel of immunohistochemical stains (CD45RO, CD45RA, CD43, CD3, CD20, CD30, CD68, and HLA-DR), 8 cases demonstrated unequivocal B-cell phenotype and 3 cases had equivocal or weak staining patterns for B-cell markers. We identified no cases of T-cell lymphoma. Of 7 cases that had bone marrow biopsies for staging, 3 were positive morphologically for bone marrow involvement. Molecular analysis of B- and T-cell gene rearrangement was used to exclude bone marrow involvement in one case with bone marrow lymphoid aggregates and to confirm negativity in a case that was morphologically negative. Of the 11 secondary breast lymphomas, 5 were diffuse large B-cell lymphomas; 1 was diffuse large B-cell, primary mediastinal subtype; and 5 were follicle center lymphomas. Conclusions.—Breast lymphomas represented 1.2% of all non-Hodgkin lymphomas in this study; the frequency of primary and secondary cases was equal. In both groups, right breast lesions were predominant, and the most frequent morphologic type was diffuse large B-cell lymphoma. Gene rearrangement analysis is helpful in selected cases to rule out bone marrow involvement, especially in older patients, in whom lymphoid aggregates are common.

Composite Nodular Lymphocyte-Predominance Hodgkin Disease and γ-Heavy-Chain Disease

2001 ◽  
Vol 125 (6) ◽  
pp. 803-807
Author(s):  
S. David Hudnall ◽  
Jack B. Alperin ◽  
John R. Petersen
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
B Cell ◽  
Heavy Chain ◽  
Monoclonal Gammopathy ◽  
Hodgkin Disease ◽  
Graves Disease ◽  
Unique Case ◽  
History Of ◽  
Heavy Chain Disease

Abstract The association of Hodgkin disease with monoclonal gammopathy has rarely been reported. We present a case of a 48-year-old woman with a history of autoimmune hemolytic anemia and Graves disease who presented with hepatosplenomegaly and a γ-heavy-chain paraprotein. Histopathology of lymph node and bone marrow revealed nodular lymphocyte-predominance Hodgkin disease, while examination of the spleen revealed plasmacytosis consistent with γ-heavy-chain disease. Following splenectomy, the patient has remained in complete remission for both conditions with no further treatment. To our knowledge, this is the first report of a patient with both γ-heavy-chain disease and nodular lymphocyte-predominance Hodgkin disease. Given recent data indicating the B-cell nature of this form of Hodgkin disease, the authors propose that in this unique case there may be a clonal relationship between these 2 concurrent B-cell lymphoproliferative processes.

Evaluation of Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) in Patients with Non-Hodgkin’s Lymphoma (NHL) Having Previously Received Autologous Stem Cell Transplant (ASCT).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5238-5238 ◽  
Author(s):  
Samuel A. Jacobs ◽  
Barry McCook ◽  
Frank Torok ◽  
Norbert Avril ◽  
Nick Vidnovic ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
B Cell ◽  
Cell Lymphoma ◽  
Prior History ◽  
Ibritumomab Tiuxetan ◽  
Heavily Pretreated ◽  
History Of ◽  
Lymphomatous Involvement ◽  
Yttrium 90

Abstract Background: As the first radioimmunotherapeutic (RIT) agent approved for the treatment of relapsed or refractory B-cell NHL, yttrium 90 (90Y) ibritumomab tiuxetan (Zevalin®) has been shown to achieve durable responses in heavily pretreated NHL patients. In phase 1–2, the eligibility criteria for 90Y ibritumomab tiuxetan therapy excluded patients with hypocellular bone marrow (<15%), lymphomatous involvement >25%, or prior ASCT due to concern of depleting the bone marrow reserve. However, Kaminski et al previously demonstrated that a parallel RIT agent, 131I tositumomab, was safe and efficacious when administered after ASCT (Blood2000; 96:1259–66). We report our experience of using ibritumomab tiuxetan in NHL patients with a prior history of ASCT. Methods: Patients with histologically confirmed relapsed or refractory B-cell NHL, ≥18 years, platelet counts >100,000/mm3, bone marrow cellularity >15%, and lymphomatous involvement <25% were eligible for treatment. In a series of 40 patients treated with ibritumomab tiuxetan at the UPMC Cancer Center, 6 patients with prior ASCT were treated. A standard course of ibritumomab tiuxetan was given, with the therapeutic dose of 90Y ibritumomab tiuxetan administered at 0.3 mCi/kg (the initial patient, and another with platelet count ≥150,000/mm3) or the standard dose of 0.4 mCi/kg 90Y in the 4 remaining cases (baseline platelet count >150,000/mm3). Pretreatment diagnostic PET/CT scans were taken for all patients and evaluated for areas of lymphomatous involvement. Follow-up scans were performed approximately 12 weeks after treatment to assess patient response. Maximum toxicities were monitored weekly over a 12-week period after therapy and classified according to CTCAE v. 3.0 toxicity criteria. Results: Patients with a prior history of ASCT had received a minimum of 4 previous regimens (range, 4–7). Subjects presented with follicular NHL (n = 3), transformed NHL (n = 1), large cell lymphoma (n = 1), and mantle cell lymphoma (n = 1). Six patients were evaluable for toxicity and 5 patients were evaluable for response. Observed toxicities were consistent with those expected in this patient population, with 33% (2/6) and 17% (1/6) of patients experiencing grade 4 thrombocytopenia and grade 3 neutropenia, respectively. Episodes of bleeding or neutropenic fever were not observed. Of the 5 patients evaluable for response, 1 patient with follicular lymphoma had a complete response to ibritumomab tiuxetan as determined by FDG-PET imaging. Conclusions: Ibritumomab tiuxetan therapy is feasible and safe in NHL patients who have previously received ASCT. Heavily pretreated patients can benefit from the administration of ibritumomab tiuxetan although additional data are needed to further characterize the degree of clinical response after ASCT.

Gene Expression Profiling Distinguishes Waldenstrom's Macroglobulinemia Patients Presenting with Familial Disease, Advanced IPSS Prognostic Score, and Previous Treatment with Rituximab.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3930-3930 ◽  
Author(s):  
Zachary Hunter ◽  
Evdoxia Hatjiharissi ◽  
Jenny Sun ◽  
Yang Cao ◽  
Hsiuyi Tseng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Family History ◽  
B Cell ◽  
G Protein ◽  
Expression Profiling ◽  
Prognostic Score ◽  
G Protein Coupled Receptors ◽  
History Of ◽  
G Protein Coupled

Abstract Abstract 3930 Poster Board III-866 Background The use of gene expression profiling (GEP) was used to dissect the molecular profile of Waldenstrom's macroglobulinemia. Bone marrow CD19+ cells from 22 WM patients and 8 healthy donor (HD) were used in these studies, with application of analytics geared toward non-normally distributed data. Patient characteristics were as follows: median age 64 years; bone marrow disease involvement 35%; serum IgM 3,295 mg/dl; beta-2 microglobulin (B2M) 2.7 mg/L; WM ISS Prognostic Score 2. Four patients (18%) previously received rituximab, and 4 (18%) patients had a family history of WM and/or related B-cell disorders. Materials and Methods GEP was performed using the Affymetrix U133 plus 2 platform on CD19+ selected, CD138 depleted bone marrow cells. Array quality checks, normalization, and unsupervised hierarchical clustering were conducted using dChip (Li and Wong 2001 PNAS). These results were then used for further analysis via custom perl scripts that used 10,000 resampled groups to calculate bootstrap percentile based 95% confidence intervals (CI) for both mean and median values. Comparisons between groups were evaluated using approximate permutation testing. To help identify potential biomarkers, absence/presence calls from DCHIP based on the perfect match vs. mismatch comparisons were tabulated for each group and the contingency table resulting from group comparisons were analyzed using a Fisher's exact test. A gene was considered significant if 50% of its probes displayed at least a 2-fold change, mutual exclusion of means/median values and respective 95% CI, and p < 0.01 for both mean and median comparisons. This data was then compared with dChip clustering results and analyzed using Ingenuity Pathway Analysis (Ingenuity Systems). Results Significantly down regulated genes included DLL1 (-13.5 fold, expressed 0% WM vs. 88% HD, P<0.0001), LILRB5 (-13.9 fold expressed in 5% WM vs. 62% HD, P=0.003), MXD1 (-10.3 fold), FOSL2 (-8.8 fold), CXCL12 (-8.0 fold), and ATF3 (-7.5 fold). Up-regulated genes included a number of G-protein coupled receptors including LPAR5 (+7.3 fold), CYSLTR1 (+6.8 fold), and GPER (+16 fold). Other genes of interest included TLR9 (+3.9 fold), TLR10 (+2.8 fold), along with several anti-viral proteins including RANSEL (+6.9 fold), OAS1 (+7.8 fold), and OAS2 (+2.3 fold). Subgroup analysis revealed an up regulation of GP5 (+3.5 fold), LHX1 (+3.3 fold), ERG1 (+3.2 fold), FZD1 (+2.6 fold), and EFNB2 (+2.2 fold) in patients with a family history of WM and/or related B-cell disorders. For those with a high ISS score (≥3), we observed differences in WNT5A (+5.04 fold), CXCL12 (+3.5 fold), NOTCH4 (-2.6 fold) and IL2RA (-2.6 fold). Lastly, WM patients previously treated with rituximab displayed increased expression of BTG2 (+2.3 fold), MCL2 (+2.5 fold), and ARMCX2 (+5.5 fold). Conclusions The results of these studies demonstrate differential expression of several novel genes in WM including g protein coupled receptors and genes involved in interferon signaling. Importantly, these studies demonstrate for the first time differential expression of several gene candidates involved in B-cell differentiation that distinguish sporadic versus familial WM. Moreover, GEP revealed a unique profile for patients presenting with poor prognostic disease. Lastly, these studies reveal the up-regulation of 2 tumor suppressor genes, and the anti-apoptotic gene MCL-2 in WM patients treated with rituximab. The findings of these studies therefore have important implications in the pathogenesis, prognostication and treatment of WM. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The stromal composition of malignant lymphoid aggregates in bone marrow: variations in architecture and phenotype in different B-cell tumours

2002 ◽  
Vol 117 (3) ◽  
pp. 569-576 ◽  
Author(s):  
Francisco Vega ◽  
L. Jeffrey Medeiros ◽  
Wen-Hua Lang ◽  
Adnan Mansoor ◽  
Carlos Bueso-Ramos ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Lymphoid Aggregates

Survival after Autologous Transplantation to Treat Diffuse Large B-Cell Lymphoma with a History of CNS Involvement, Bone Marrow Involvement, or Histologic Transformation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5237-5237
Author(s):  
Brandon Hayes-Lattin ◽  
Pritesh Mehta ◽  
Adam Dunn ◽  
Nan Subbiah ◽  
Jose F. Leis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Autologous Transplantation ◽  
B Cell Lymphoma ◽  
Cns Involvement ◽  
Large B Cell Lymphoma ◽  
History Of ◽  
Large B Cell

Abstract Background: Patients with diffuse large B-cell lymphoma (DLBCL) who present with extra-nodal involvement or histologic transformation from low-grade disease have lower rates of survival after conventional-dose therapy. The impact of these features on outcomes after high-dose therapy with autologous transplantation was investigated. Methods: We retrospectively reviewed the outcomes of 64 consecutive patients receiving autologous transplantation from 1995 to 2003 for the treatment of DLBCL. Variables considered were age, gender, histologic transformation, history of bone marrow involvement, history of central nervous system (CNS) involvement, time from diagnosis to transplant, number of pre-transplant regimens, chemosensitivity prior to transplant, conditioning regimen, year of transplant, and the use of peripheral blood or bone marrow stem cells. Survivals were estimated by the Kaplan-Meier method. The Cox proportional hazards regression model was used to test the significance of factors on survival. Univariate association between variables and survival were tested by the log-rank test. Correlation between variables was tested with Spearman’s rank coefficient. Results: The median age at transplant among 64 patients was 53.5 years (17–74). The median overall survival was 3.3 years. Among these patients, 12 had a history of CNS involvement, 10 had a history of bone marrow involvement, and 12 had transformed from low-grade lymphoma. A Cox regression model suggested age <50 (log-rank, p=0.093), <2 regimens prior to transplant (log-rank, p=0.052), and the lack of BEAM as conditioning regimen (log-rank, p=0.019) as multivariate factors for survival. However, the use of BEAM was highly associated with older age (R²= 0.42, p=0.001) and more prior chemotherapy regimens (R²=0.24, p=0.054). A history of extranodal involvement, including prior CNS involvement (p=0.842) or bone marrow involvement (p=0.518), was not associated with lower survival by univariate analysis. No significant association was found between survival and a history of transformation (p=0.484). Conclusions: A history of CNS involvement, bone marrow involvement, or histologic transformation is not associated with lower rates of survival among patients undergoing autologous transplantation for diffuse large B-cell lymphoma at our institution. Patients who present with such histories remain candidates for autologous transplantation.

T-cell lymphoid aggregates in bone marrow after rituximab therapy for B-cell follicular lymphoma: a marker of therapeutic efficacy?

2008 ◽  
Vol 39 (2) ◽  
pp. 194-200 ◽  
Author(s):  
Pierre Raynaud ◽  
Sylvie Caulet-Maugendre ◽  
Charles Foussard ◽  
Gilles Salles ◽  
Anne Moreau ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Therapeutic Efficacy ◽  
Lymphoid Aggregates
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