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Watchful waiting (WW) is one of the standard approaches for newly diagnosed follicular lymphoma (FL) patients with low‐tumor burden. However, the impact of WW in FL patients at the first progression, remains unclear. We reviewed 206 FL patients who experienced the first progression after responding to the initial treatment at our institution between 1998 and 2017. Patients were classified into either the WW cohort (132 patients) or the immediate treatment cohort (74 patients). Overall, the median follow‐up from the first progression was 79.8 months (range, 2.1–227.0 months). In the WW cohort, the estimated median time to next treatment (TNT) was 19.7 months (95% confidence interval [CI], 13.4–30.2), and 76.5% (95% CI, 68.0–84.1) of the patients subsequently underwent the second‐line treatment at 5 years. There was a significant difference in the median time to treatment failure in the WW cohort (72.8 months; 95% CI, 64.6–94.0) compared to the immediate treatment cohort (23.3 months; 95% CI, 13.4–38.8) (HR, 2.13; 95% CI, 1.48–3.06), whereas overall survival and the cumulative incidence of histological transformation were not significantly different between two cohorts. In a multivariate analysis, rituximab refractory status, progression of disease within 24 months from the induction of first‐line therapy, and a high Follicular Lymphoma International Prognostic Index score at diagnosis were significantly associated with shorter TNT. Interestingly, 15 patients (11%) of the WW cohort experienced spontaneous tumor regression during WW, and their TNT (median, 82.1 months, 95% CI, 11.7‐NA) was longer than that of the remaining patients in the WW cohort (median, 16.5 months, 95% CI, 13.0–25.4), with a significant difference (p = 0.01). The results of the present study suggested that WW could be a safe and reasonable option even at the first progression for the selected FL patients, without a negative impact on clinical outcomes. [ABSTRACT FROM AUTHOR]

Background and Aim: This study aimed to investigate the relationship between the histological type of colorectal lymphoma and its endoscopic features. Methods: We retrospectively analyzed patients with primary colorectal lymphoma who were diagnosed using colonoscopy and biopsy specimens at the National Cancer Center Hospital, Tokyo, Japan. The lesions were macroscopically classified into the following types via colonoscopy: polypoid, ulcerative, multiple lymphomatous polyposis, diffuse, and mixed. Results: A total of 117 lesions were identified in 90 patients enrolled in this study. Of these, 59 (50%) were located in the ileocecal region, 23 (20%) in the rectum, 9 (8%) in the transverse colon, 8 (7%) in the sigmoid colon, 7 (6%) in the descending colon, and 4 (3%) in the ascending colon. Moreover, the most common histological subtypes were diffuse large B‐cell lymphoma (DLBCL) in 39 patients (43%) and mantle cell lymphoma (MCL) in 23 patients (26%), followed by follicular lymphoma (FL; 17%), mucosa‐associated lymphoid tissue (MALT) lymphoma (9%), peripheral T‐cell lymphoma‐NOS (2%), monomorphic epitheliotropic intestinal T‐cell lymphoma (MEITL; 2%), and Burkitt lymphoma (1%). More than half of the DLBCL (52%), MCL (52%), and MALT (56%) lymphomas were macroscopically classified as polypoid types. In contrast, FL lesions showed various macroscopic types. The majority of DLBCL (62%) and FL (78%) lesions were distributed in the ileocecal region. MCL lesions tended to be widely spread in various sites of the large intestine. Conclusions: Colorectal lymphomas showed macroscopically distinctive features depending on the histological type. Understanding the macroscopic classification of the lesions by colonoscopy and its distribution may be helpful in diagnosing the type of lymphoma and determining the malignant grade based on the histological types. [ABSTRACT FROM AUTHOR]

This study characterized the outcomes of patients who underwent hematopoietic cell transplantation (HCT) for transformed follicular lymphoma (tFL), and clarified the association of low‐dose anti‐thymocyte globulin use with outcomes after allogeneic HCT. The retrospective study cohort included 74 consecutive patients who underwent autologous (n = 23) or allogeneic (n = 51) HCT at our center from 2000 to 2017. Compared with the allogeneic HCT group, the autologous HCT group underwent fewer systemic regimens before HCT (median 2 vs. 5, p < 0.001) and were more likely to have chemosensitive disease at HCT (100% vs. 82%, p = 0.05), while age, sex and HCT‐specific comorbidity index were similar between the two groups. With a median follow‐up of 5.8 years among survivors, the 5‐year probability of progression‐free survival was 64% after autologous HCT and 55% after allogeneic HCT (p = 0.21). The 5‐year cumulative incidence of non‐relapse mortality was 0% after autologous HCT and 9.5% after allogeneic HCT (p = 0.062). The 5‐year cumulative incidence of disease progression was similar between autologous and allogeneic HCT (36% vs. 36%, respectively, p = 0.88). In the allogeneic HCT group, the use of low‐dose anti‐thymocyte globulin was associated with a lower incidence of severe acute GVHD but not with an increased risk of mortality or disease progression. More than half of patients with early phase chemosensitive tFL and approximately half of those with advanced‐phase tFL achieved long‐term progression‐free survival with autologous and allogeneic HCT, respectively. Disease progression was the major cause of treatment failure after both types of HCT. Further strategies are needed to reduce the risk of disease progression. [ABSTRACT FROM AUTHOR]

The diagnosis of histological transformation of follicular lymphoma can be challenging and ambiguous. We investigated the distribution of the Ki‐67 labeling index of histological transformation of follicular lymphoma and determined its cutoff value to predict poor outcomes. The diagnostic criteria for histological transformation were a diffuse pattern of proliferation and a proportion of large lymphoma cells ≥20%. Of the 1121 patients with follicular lymphoma, 171 (15%) showed histological transformation to diffuse large B‐cell lymphoma. Of these, 76 patients, whose biopsies were obtained from the sites with the highest maximum standardized uptake values, according to the positron emission tomography findings, were included. The Ki‐67 index ranged from 16.8% to 98.4% (median, 60.6%). In patients with histological transformation, the most significant differences were found in progression‐free survival (p = 0.087, 58% vs. 87% at 2 years) and overall survival (p = 0.024, 53% vs. 85% at 5 years) when a 70% cutoff was used. Additionally, overall survival was significantly shorter in patients with histological transformation with maximum standardized uptake values of ≥20 (p < 0.0001) and absence of a follicular lymphoma component (p = 0.004). A Ki‐67 index of ≥70% was a significant adverse factor for overall survival in patients with histological transformation of follicular lymphoma and may predict poor outcomes. [ABSTRACT FROM AUTHOR]

Objectives: In this study, we aimed to determine the clinicopathological factors influencing the treatment‐free period in patients with follicular lymphoma (FL) using a watch‐and‐wait (WW) strategy. Methods: We retrospectively assessed histopathological parameters of 82 patients with FL. Results: The median time from diagnosis to WW discontinuation was 62 months (range, 3‐138), and median follow‐up was 86 months (range, 3‐183). Intermediate or high‐risk Follicular Lymphoma International Prognostic Index score (P =.012), non‐duodenal‐type (P =.011), higher numbers of interfollicular CD4+ (P =.038) and intrafollicular FOXP3+ cells (P =.024) in the tumor microenvironment, and Ki‐67 index ≥10% (P =.031) were significant adverse factors for WW discontinuation in univariate analyses. Conclusion: Patients with adverse factors for WW discontinuation should be carefully observed during follow‐up. [ABSTRACT FROM AUTHOR]

Although histologic analysis is the gold standard for diagnosing follicular lymphoma (FL) transformation, many patients are diagnosed with transformation by clinical factors as biopsy specimens often cannot be obtained. Despite the frequency of clinical diagnosis, no clinical assessment tool has yet been established for FL transformation in the rituximab era. We derived and validated a transformation scoring system (TSS) based on retrospective analyses of 126 patients with biopsy‐proven FL and histologic transformation (HT) at two hospitals of the National Cancer Center of Japan. In the derivation set (76 patients), the detailed analyses of the clinical characteristics at disease progression showed that lactate dehydrogenase (LDH) elevation, focal lymph nodal (LN) enlargement, hemoglobin <12 g/dl, and poor performance status (PS) (2‐4) were associated with HT. The weights of these variables were decided based on the regression coefficients. Next, we constructed a TSS encompassing the above four factors: LDH, (> upper limit of normal [ULN], ≤ULN ×2) (1 point), (≥ULN ×2) (2 points); focal LN enlargement, (≥3 cm, <7 cm) (1 point), (≥7 cm) (2 points); hemoglobin <12 g/dl (1 point); poor PS (2 points). We identified a high positive predictive value (PPV) (96.4%) and negative predictive value (NPV) (85.4%) for diagnosing HT when a cutoff score of 2 was selected for our TSS. In an external validation set (50 patients), the probability of HT was high with scores ≥2 (PPV, 93.3%; NPV, 82.9%). We developed a TSS that offers a simple, yet, valuable tool, for diagnosing HT, especially in patients who cannot undergo biopsy. [ABSTRACT FROM AUTHOR]

CD20− change after rituximab-containing therapy is considered one of the main reasons of rituximab resistance of B-cell non-Hodgkin lymphomas (B-NHLs). However, the clinicopathological characteristics of B-NHL with CD20− change are not entirely understood. In this study, 252 B-NHL patients who were CD20+ at initial diagnosis, whose diseases relapsed or were refractory after rituximab-containing therapy, and who were re-biopsied between 2000 and 2018, were included. The median number of rituximab administration was 11 (range, 1–48). Completely negative (cCD20−) and partially negative (pCD20−) change of CD20 was observed in 49 (20%) and 16 (6%) cases, respectively. Among cCD20− and pCD20− cases, 74% and 62% of the cases changed to CD20− at the second relapse or later, respectively. Overall survival was significantly shorter in cCD20− follicular lymphoma (FL) cases than in CD20+ FL cases. Seven histopathological patterns, such as CD20− change without histological change, histological transformation (HT) to CD20− diffuse large B-cell lymphoma, and proliferation of plasmablastic/plasmacytoid tumor cells, were associated with CD20− change. HT occurred more frequently in FLs with CD20− change than in FLs continuously expressing CD20 (P < 0.0001), regardless of the timing of HT. Nine out of 25 cases (36%) showed regain or heterogeneous regain of CD20 expression. In conclusion, 20% and 6% of the 252 B-NHL cases show cCD20− and pCD20− changes with 7 histological patterns after rituximab-containing therapy. Because changes in morphology and CD20 expression after rituximab-containing therapy vary, and recovery of CD20 expression is not rare, careful follow-up and re-biopsy in B-NHL patients are recommended. [ABSTRACT FROM AUTHOR]

This study aimed to indicate patient outcomes and pathological characteristics of follicular lymphoma (FL) with peripheral blood (PB) involvement. Of 533 patients with FL, 56 (11%) had PB involvement. Of the patients treated with rituximab, 39 patients with PB involvement had significantly shorter progression-free survival than 107 patients with stage IV disease without PB involvement ( p = 0.021), but the overall survival was not different ( p = 0.804). The histopathology of the primary sites was usually nodal (95%) low-grade (86%) FL with IGH/BCL2 fusion (75%). Flow cytometric and immunohistochemical analyses revealed that the incidence of CD10 positivity was lower in the bone marrow (55% and 58%) and PB (41% and not available) than in the primary site (86% and 93%) ( p = 0.004 and p = 0.0001, respectively). Therefore, even if small lymphoma cells in the bone marrow and PB are negative for CD10, FL cannot be ruled out. [ABSTRACT FROM AUTHOR]

We report four cases of exceptional follicular lymphoma (FL) showing marked monocytoid or plasmacytoid differentiation and tiny or indistinct follicles, mimicking marginal zone lymphoma or plasma cell neoplasm. The lymphoma of patient 2 had lymphoepithelial lesions. The lymphoma of patient 4, who had a history of typical FL, was composed of only monocytoid cells, suggesting secondary involvement of the monocytoid component of FL. The lymphomas of patients 1 and 2 had tiny follicles immunoreactive with CD10 and BCL-2, whereas samples from patients 3 and 4 were negative for CD10. Fluorescence in situ hybridization (FISH) analysis showed IGH/BCL2 fusion in three of the four lymphomas (patients 1, 3, and 4). Histological analysis showed time- and site-dependent differences in FL characteristics in patients 2 and 4. Identifying tiny CD10++/BCL-2++ neoplastic follicles, detecting IGH/BCL2 fusion by FISH, and considering a history of FL are crucial for diagnosing such exceptional cases of FL. [ABSTRACT FROM AUTHOR]