scholarly journals Follicular lymphoma in situ in intra-abdominal lymphadenectomies- a study of 5 cases: revisiting the entity

2015 ◽  
Vol 1 (1) ◽  
pp. 62
Author(s):  
Rinsey R Kurian ◽  
Thiagarajah Balamurugan ◽  
Bruno Ping ◽  
Louise Hendry ◽  
Stephen Whitaker ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Incidental Finding ◽  
B Cell Lymphoma ◽  
Clinical Settings ◽  
Follicular Hyperplasia ◽  
Lymphoid Malignancies ◽  
Clinically Significant ◽  
Age Range

<p><strong>Background</strong>: Follicular lymphoma <em>in situ</em> (FLIS) is characterized by the presence of germinal centers that strongly express BCL-2 protein and germinal center markers CD10 and BCL-6, although most of the remaining lymph node shows a pattern of follicular hyperplasia, in the absence of interfollicular infiltration. Here, we present five cases of FLIS and discuss their presentation and pathological identification in a wide variety of clinical settings. <strong>Materials and Methods</strong>:<strong> </strong>The present study includes five cases of FLIS diagnosed in the department of surgical pathology over a period of three years (2010 to 2013). The clinical data and the follow-up information were obtained from the medical records. <strong>Results</strong>: The present study included three male and two female patients with an age range of 46–72 years. One case of FLIS was associated with diffuse large B-cell lymphoma (DLBCL), while in two cases this was an incidental finding associated with other non-lymphoid malignancies. <strong>Conclusion</strong>: FLIS has a very low rate of progression to clinically significant follicular lymphoma (FL), and the management strategy recommended is to watch and wait. However, some cases may develop into full blown FL and also many non-FL lymphoid malignancies have been seen associated with it. Hence, a staging workup is strongly advocated by many authors for FLIS.</p>

scholarly journals Follicular lymphoma in situ: clinical implications and comparisons with partial involvement by follicular lymphoma

Blood ◽  
2011 ◽  
Vol 118 (11) ◽  
pp. 2976-2984 ◽  
Author(s):  
Armin G. Jegalian ◽  
Franziska C. Eberle ◽  
Svetlana D. Pack ◽  
Mariya Mirvis ◽  
Mark Raffeld ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Gene Rearrangement ◽  
Incidental Finding ◽  
Clinical Implications ◽  
Rate Of Progression ◽  
Reactive Lymph Node ◽  
Local Radiation ◽  
Clinically Significant

Abstract Follicular lymphoma in situ (FLIS) was first described nearly a decade ago, but its clinical significance remains uncertain. We reevaluated our original series and more recently diagnosed cases to develop criteria for the distinction of FLIS from partial involvement by follicular lymphoma (PFL). A total of 34 cases of FLIS were identified, most often as an incidental finding in a reactive lymph node. Six of 34 patients had prior or concurrent FL, and 5 of 34 had FLIS composite with another lymphoma. Of patients with negative staging at diagnosis and available follow-up (21 patients), only one (5%) developed FL (follow-up: median, 41 months; range, 10-118 months). Follow-up was not available in 2 cases. Fluorescence in situ hybridization for BCL2 gene rearrangement was positive in all 17 cases tested. PFL patients were more likely to develop FL, diagnosed in 9 of 17 (53%) who were untreated. Six patients with PFL were treated with local radiation therapy (4) or rituximab (2) and remained with no evidence of disease. FLIS can be reliably distinguished from PFL and has a very low rate of progression to clinically significant FL. FLIS may represent the tissue counterpart of circulating t(14;18)-positive B cells.

Favorable Results of Rituximab in Combination with CHOP in the Front-Line Treatment of Follicular Lymphoma Grade 3.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2770-2770
Author(s):  
Luis Fayad ◽  
Michael Overman ◽  
Barbara Pro ◽  
Peter McLaughlin ◽  
Felipe Samaniego ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Grade 3 ◽  
Large B Cell

Background: Follicular lymphoma grade 3 has a natural history that is more akin to that of diffuse large B-cell lymphoma. The addition of rituximab to standard CHOP has resulted in improved response and survival in diffuse large B-cell lymphoma. Information about outcomes in follicular lymphoma grade 3 is lacking. Methods: A single institution retrospective review of patients with follicular grade 3 lymphoma evaluated at the UTMDACC from 1999 to 2004. Patients were located from the UTMDACC lymphoma database. All patients were initially treated with R-CHOP. Results: Forty-five patients were identified: 51% male, 47% ≥60 years, and 87% follicular grade 3b. The LDH was elevated in 24%, ECOG performance status was >1 in 2%, and >1 site of extranodal involvement was present in 10%. Stage distribution was 11% stage I, 11% stage II, 42% stage III, and 36% stage IV, bulky disease (>7cm) was present in 11%, and B symptoms occurred in 13%. Beta-2 microglobulin was elevated in 57% with values >3 μg/dL in over 50%. IPI distribution was: 46% IPI Low, 38% LI, 11% IH, and 4% IPI High. Overall response rate was 100% with 96% complete responses. Relapse rate by IPI category was 24% for Low IPI, 18% for IPI LI, and 40% for IPI IH, and 100% for the two patients with High IPI. With median follow-up of 33 months, three year failure-free survival (FFS) is 73% (95% CI: 59 to 87%). One patient died (2%) with an overall survival (OS) at three years of 97% (95% CI: 93 to 100%). Conclusion: The addition of rituximab to CHOP provided a high response rate and excellent early survival in this group of mostly good prognosis patients. Relapses were still seen; longer follow-up is needed.

Rituximab Fails to Reduce Histologic Transformation (HT) Rate of Follicular Lymphoma (FL) to Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 837-837 ◽  
Author(s):  
Ariel E Marciscano ◽  
Neel Gupta ◽  
Zhigang Zhang ◽  
Julie Teruya-Feldstein ◽  
Ariela Noy
Keyword(s):  
Follicular Lymphoma ◽  
Lower Risk ◽  
Cell Lymphoma ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
P Value ◽  
First Line ◽  
First Line Therapy ◽  
Large B Cell Lymphoma

Abstract Background: Histologic Transformation (HT) of indolent follicular lymphoma to aggressive lymphoma is a critical and sometimes fatal event in a patient’s disease course. It is unclear if rituximab influences HT. We have previously shown that single agent rituximab is used earlier in the disease course than traditional chemotherapy likely due to rituximab’s high therapeutic index (Cohler et al., ASH 2007). Others have shown rituximab also improves the complete response rate, disease free and overall survival of follicular lymphoma when used as a single agent and in combination with chemotherapy. Theoretically, this could reduce the disease burden over a patient’s lifetime and consequently the transformation rate. Methods: We retrospectively screened 3500 patients and identified 584 eligible patients at Memorial Sloan Kettering Cancer Center (MSKCC) with newly diagnosed, treatment naïve, indolent follicular lymphoma. We compared two cohorts of rituximab usage: 1998– 2000 and 2001–2006. In the former, patients received rituximab predominantly in the relapsed setting. In the latter, patients liberally received rituximab even as single agent first line therapy. Histologic transformation to diffuse large B cell lymphoma (DLBCL) was the primary study endpoint. All therapy was recorded. Results: Median follow-up time was 92 months for the 1998–2000 cohort and 41 months for the 2001–2006 cohort. Patients in the latter cohort received rituximab both earlier in the course of follow up and more often as a first line therapy. The median time from diagnosis to first rituximab was 21 months vs. 2 months, respectively. Rituximab was given alone or in combination as first line systemic therapy to 36% of the 1998–2000 cohort, but to 93% of the 2001–2006 cohort. The comparative risks of transformation between the two cohorts were not statistically significant (P-value = 0.41 by log rank comparison). The cumulative incidence of transformation 36 months after diagnosis was 8.1% for the 1998– 2000 cohort and 4.4% for the 2001–2006 cohort. Furthermore, patients receiving rituximab first line, either single agent or in combination, compared to patients receiving rituximab as salvage therapy, showed essentially no difference in risk of histologic transformation. (P-value = 0.68) Surprisingly, patients never receiving rituximab had a significantly lower risk of transformation than those who received rituximab at any point (p-value = 0.0095), however, these rituximab naïve patients had lower risk FLIPI scores accounting for the difference (p-value = 0.15). Notably, 173/584 patients never received systemic therapy, and 102 of these were expectantly monitored without any local therapy, such as radiotherapy or therapeutic surgery). None of these 102 patients had transformation within the first 36-months of follow up. Finally, we confirm Ginè et al.’s earlier finding that a higher risk FLIPI score confers a higher risk of transformation. (Annals of Oncology, 2006) For each unit increase of FLIPI risk score (e.g., 3 à 4), the probability of histologic transformation at any time point increases 1.72 fold. Moreover, high-risk FLIPI patients (3–5 risk factors) have a 3.3-fold increase in risk of HT (p-value <0.0001). Conclusions: Patients diagnosed with FL in 2001–2006 received rituximab earlier in their disease and more frequently than those diagnosed in 1998–2000. However, in contrast to our hypothesis, this did not translate to a lower risk of transformation for the 2001– 2006 cohort. The 36-month risk of transformation was lower in patients with lower FLIPI scores. This data supports the clinical decision to expectantly monitor low-risk FLIPI patients.

Concurrent Follicular Lymphoma At Diagnosis Has a Negative Impact On The Outcome Of Patients With Diffuse Large B Cell Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4260-4260 ◽  
Author(s):  
David Wrench ◽  
Hasan Rizvi ◽  
Andrew Wilson ◽  
Ciaran O'Riain ◽  
Andrew Clear ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Negative Impact ◽  
Tissue Sample ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract In contrast to either de novo diffuse large B cell lymphoma (dnDLBCL) or follicular lymphoma (FL) that transforms to DLBCL, the clinical course of DLBCL and FL presenting simultaneously (DLBCL/FL) is not well characterised. From 1 October 1975 to 31 December 2010, 819 patients were diagnosed with DLBCL at St Bartholomew’s Hospital. Twenty-seven patients with bone marrow (BM) involvement were excluded because of histologies other than FL or DLBCL in the BM (n=2) or unavailable BM samples (n=25). The remaining patients comprised the study population (n=792) which consisted of 45 histologically confirmed DLBCL/FL and 747 dnDLBCL. A pathological review was performed of all DLBCL/FL and all the positive BM samples. Remission duration (RD), progression-free survival (PFS), overall survival (OS) and lymphoma-specific survival (LSS) were compared in DLBCL/FL and dnDLBCL. DLBCL/FL comprised composite (both histologies in the same tissue sample; n=24) and discordant (both histologies in separate tissue samples; n=21) lymphoma. The majority (n=18, 75%) of composite DLBCL/FL were diagnosed on lymph node (LN) sampling with the remainder identified in tonsil (n=3) with single cases in testis, salivary gland and BM. Discordant DLBCL/FL, presented as DLBCL and FL involving LN and BM respectively in 16 cases (76%). Other combinations included DLBCL and FL in separate LNs (n=2) and one each of kidney + BM, mesentery + LN, bone biopsy + BM. At presentation, DLBCL/FL had more advanced stage (p<0.01), higher IPI (p=0.02) and lower Hb (p=0.02) than dnDLBCL in keeping with BM involvement rates of 19/45 (42%) and 32/747 (4%), respectively. Most DLBCL/FL (n=42; 93%) received anthracycline based combination chemotherapy (a single case received HD-MTX and 2 cases palliative / no treatment both of whom died within 3.5 months) and, since 2003, addition of rituximab (24% of cases) to CHOP (n=10) or CODOX-M/IVAC (n=1); with similar rates of anthracycline (82%) and rituximab (29%) use in dnDLBCL. The 44 documented responses in DLCBL/FL included complete response (CR, n=26; 59% similar to 66% in 696 patients with dnDLBCL and assessable responses), partial response (n=7) and stable disease/progression (n=11) with a shorter RD for DLBCL/FL (median 8.7 yrs) compared to dnDLBCL (median not reached), although this was not statistically different (p=0.09). PFS was significantly shorter for DLBCL/FL in comparison with dnDLBCL (2.0 versus 4.6 yrs, respectively; p=0.02) and DLBCL/FL not achieving CR had inferior OS (0.4 yrs) than those achieving CR (11.5 yrs; p<0.01). Relapse after CR occurred in 12/26 (46%) patients with DLBCL/FL and in 142/456 (31%; p=0.13) of those with dnDLBCL; 83% and 87% relapsed cases have died, respectively. With a median follow-up of 10 yrs, 71% patients with DLBCL/FL have died as compared to 65% patients with dnDLBCL, and no differences in median OS were observed (4.0 yrs for DLCBL/FL versus 5.5 yrs for dnDLBCL; p=0.28). Death was most commonly due to lymphoma, the rate being similar in patients with DLBCL/FL (56%) and dnDLBCL (52%). However, LSS was shorter for DLBCL/FL (6.3 yrs) than dnDLBCL (13.8 yrs; p<0.01) and, with the long follow-up, we found no differences in OS between DLBCL with concordant (DLBCL, n=32) or discordant (FL, n=18) BM involvement (p=0.38). This study, to the authors’ knowledge the largest series of concurrent FL and DLBCL, confirms the relative frequency of DLBCL/FL to DLBCL (45:747, 6%) and demonstrates that the simultaneous presence of FL negatively influences the outcome of patients with DLBCL, by shortening PFS and LSS. This data emphasizes the importance of thorough staging at diagnosis, including BM biopsies, and highlights the need for better management of this population, which has a worse prognosis than dnDLBCL and is frequently excluded from clinical trials. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A Prospective Analysis of Erythrocyte Membrane Fatty Acid Concentrations and Risk of Non-Hodgkin Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1789-1789
Author(s):  
Brenda M. Birmann ◽  
Yu-Han Chiu ◽  
Kimberly A. Bertrand ◽  
Shumin Zhang ◽  
Francine Laden ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Follicular Lymphoma ◽  
Hodgkin Lymphoma ◽  
Trans Fatty Acids ◽  
B Cell Lymphoma ◽  
Inverse Association ◽  
Non Hodgkin Lymphoma ◽  
Clear Association

Abstract Introduction: Circulating fatty acids, which can serve as biomarkers of diet or activity of specific metabolic pathways, may influence non-Hodgkin lymphoma (NHL) risk by modulating inflammation or lymphocyte membrane stability. We performed prospective studies to evaluate red blood cell (RBC) membrane fatty acids as biomarkers of future NHL risk, hypothesizing a positive association for RBC saturated and trans fatty acids and an inverse association for polyunsaturated fatty acids (PUFAs) with risk of NHL and major NHL subtypes. Methods: We conducted a nested case-control study among Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS) participants who provided blood samples in 1989-90 (NHS) or 1993-4 (HPFS). We confirmed 583 incident NHL cases through 2010 and matched one control per case on age, gender, race, and blood draw date. By gas chromatography we identified and determined membrane concentrations of 33 individual fatty acids in RBCs. We estimated the odds ratio (OR) and 95% confidence interval (CI) of NHL per 1 standard deviation (SD) increase in RBC level of specific fatty acids using unconditional logistic regression adjusted for matching factors. We also analyzed three common B-NHL subtypes individually (chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma) and examined all B-NHLs in aggregate with and without CLL/SLL. Results: We observed no associations between specific fatty acids and NHL risk overall (data not shown). In subtype-specific analyses, RBC very long chain saturated fatty acid (VLCSFA) levels (including the 20:0, 22:0, 23:0 fatty acids) were inversely associated with the group of all B-NHLs except CLL/SLL, with ORs suggesting 18% to 19% decreases in risk per SD increase in concentration (Table 1). We observed suggestive inverse associations of similar magnitude for follicular lymphoma and DLBCL but no clear association with CLL/SLL for these 3 VLCSFAs (Table 1). These three VLCSFAs had moderate to strong pairwise correlations; Spearman correlations were 0.61 for 20:0 with 22:0, 0.42 for 20:0 with 23:0 and 0.64 for 22:0 with 23:0. PUFAs were also inversely associated with all B-NHL except CLL/SLL, a finding primarily driven by RBC arachidonic acid levels [OR (95%CI) per SD: 0.83 (0.71, 0.90)] and suggestive also for follicular lymphoma [OR, 95% CI per SD: 0.79 (0.61, 1.02)] and DLBCL [OR, 95% CI per SD: 0.82 (0.64, 1.06)]. The remaining RBC fatty acids, including trans fatty acids, had no clear association with any NHL endpoint (data not shown). We did not observe heterogeneity by follow-up interval or age, although we had limited statistical power to detect significant heterogeneity for specific NHL subtypes. Conclusion: RBC levels of VLCSFAs and PUFAs may be associated with lower risk of several types of B-NHL other than CLL/SLL. The specific fatty acids found to be related with NHL risk are not good biomarkers of diet, suggesting that the observed relations may instead be due to endogenous metabolic processes. Investigation is warranted into biologic mechanisms by which circulating fatty acids and their determinants may influence NHL risk, as is further examination of these associations in larger (ideally pooled) study populations. Disclosures No relevant conflicts of interest to declare.

A Clinicopathologic Evaluation of Follicular Lymphoma Grade 3A Versus Grade 3B Reveals No Survival Differences

2004 ◽  
Vol 128 (8) ◽  
pp. 863-868
Author(s):  
Eric D. Hsi ◽  
Imran Mirza ◽  
Gerard Lozanski ◽  
John Hill ◽  
Brad Pohlman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Follicular Lymphoma ◽  
B Cell Lymphoma ◽  
Wilcoxon Test ◽  
World Health ◽  
Fisher Exact Test ◽  
Lower Grade ◽  
Significant Difference ◽  
Grade 3

Abstract Context.—The World Health Organization classification recommends categorizing grade 3 follicular lymphomas based on the presence of centrocytes (grade 3A) or of sheets of centroblasts (grade 3B). The clinical significance of this practice is not known. Objective.—To determine whether grade 3 follicular lymphoma subtype is associated with prognosis. Design.—Multi-institutional retrospective case series. Main Outcome Measure.—Overall survival. Results.—Forty-five cases of grade 3 follicular lymphoma without diffuse large B-cell lymphoma were studied (35 cases of grade 3A, 10 cases of grade 3B) from 21 men and 24 women (median age, 67 years; mean age, 63.8 years; range, 26–86 years). Follow-up information from the time of diagnosis was available in all patients, with a median follow-up time of 24 months (mean, 34 months; range, 2– 115 months). Treatment information was available in 40 patients. There was no difference in age (P = .45, Wilcoxon test) or stage (P = .76, Fisher exact test) between patients with follicular lymphoma of grade 3A or grade 3B. Furthermore, the Cochran-Armitage test for trends showed no evidence that the proportion of patients with follicular lymphoma grade 3A or 3B increased or decreased with increasing stage at presentation. Kaplan-Meier analysis showed a median overall survival of 44 months from the time grade 3 follicular lymphoma was diagnosed, with no significant difference between cases diagnosed as grade 3A or grade 3B (P = .14, log-rank test). Univariable Cox proportional hazards modeling showed no evidence that an anthracycline-containing chemotherapy regimen or history of lower grade follicular lymphoma affected overall survival. Conclusions.—In this retrospective series, subclassification of grade 3 follicular lymphoma into type 3A and 3B categories had limited clinical and prognostic significance. However, the study was limited by lack of statistical power. Since morphology often provides clues for progress in defining biologic differences, subtyping may still be useful, particularly in the setting of prospective clinical studies.

One Patient, Two Lymphomas

2004 ◽  
Vol 128 (9) ◽  
pp. 1035-1038 ◽  
Author(s):  
Zuoqin Tang ◽  
Wen Jing ◽  
Neal Lindeman ◽  
Nancy Lee Harris ◽  
Judith A. Ferry
Keyword(s):  
Follicular Lymphoma ◽  
Lymphoid Tissue ◽  
Gastrointestinal Endoscopy ◽  
B Cell Lymphoma ◽  
Tissue Type ◽  
Gastric Disease ◽  
Upper Gastrointestinal Endoscopy ◽  
H Pylori ◽  
Upper Gastrointestinal

Abstract We report the case of a 73-year-old man who presented with a 2- to 3-month history of epigastric discomfort and guaiac-positive stool. An upper gastrointestinal endoscopy revealed a diffuse erythematous nodular mucosa and submucosal thickening in the stomach. Diffuse mucosal nodularity was also found in the second portion of the duodenum. A complete workup with histologic, immunohistochemical, and molecular studies revealed 2 distinct, apparently unrelated lymphomas, namely, a gastric marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue type) in a background of Helicobacter pylori gastritis and a grade 1/3 duodenal follicular lymphoma. The patient was then treated with an H pylori eradication regimen. No therapy was given for his duodenal follicular lymphoma because his symptoms were thought to be due to the gastric disease and because the duodenal lesion was small. A 6-month follow-up with upper gastrointestinal endoscopy revealed only focal biopsy scarring in the stomach and an apparently normal duodenum. The follow-up biopsies revealed significant regression of his mucosa-associated lymphoid tissue lymphoma, but persistence of his duodenal follicular lymphoma. The combination of these 2 lymphomas in the same patient and the different clinical responses to antibiotic treatment make this case unique.

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