Expression of CD68+ tumor-associated macrophages in patients with diffuse large B-cell lymphoma and its relation to prognosis

Tumor-associated macrophages (TAM) have been ascribed both pro- and anti-tumor properties, but the majority of clinical cancer studies have shown that the presence of a high number of TAM is related to poor prognosis, suggesting that TAM predominantly exert pro-tumoral activity. The prognostic role of TAM in patients with diffuse large B-cell lymphoma (DLBCL), however, is so far unknown. Therefore, TAM were immunohistochemically stained with a CD68 antibody in a retrospective, population-based study including 176 DLBCL patients treated with curative intent. With the exception that patients >60 years of age had a larger number of CD68+ cells (1143 vs 1018 cells/mm²; P  = 0.05), no significant differences were found between the number of CD68+ cells and other clinical factors. Similarly, germinal center B-cell (GCB)/non-GCB immunophenotype or low/high Ki-67 percentage were not associated with CD68 expression. Finally, no significant correlation was found between the number of CD68+ cells and progression-free survival ( P  = 0.34) or overall survival ( P  = 0.94). These data indicate that the pro-tumor effect of TAM has limited clinical relevance in DLBCL patients, which could imply that therapeutic strategies aimed at enhancing their anti-tumor activity are of continuous clinical interest.     

Primary sacral non-germinal center type diffuse large B-cell lymphoma with MYC translocation: a case report and a review of the literature

An 85-year-old man presented with pain and numbness in the left buttock, and physical examination revealed an approximately 7 cm mass extending from the first to the third sacral vertebrae; biopsy of the mass led to the diagnosis of CD10-negative, BCL6-weakly positive, MUM1-positive, non-germinal center (non-GC) type diffuse large B-cell lymphoma (DLBCL). Furthermore, serological testing showed negative results for Epstein-Barr virus (EBV) infection, and fluorescence in situ hybridization (FISH) revealed a MYC translocation. Radiographs showed no remarkable osteolytic bone destruction, and the patient was staged with Stage IAE. After 8 cycles of rituximab therapy and 6 cycles of CHOP therapy, complete remission has been maintained until now, approximately 1 year after the treatment. Primary sacral lymphoma is very rare, with only 6 reported cases, including the present one. A review of the reported cases revealed that the disease predominantly affects elderly men, is usually non-GC-type DLBCL and stage IAE, measures approximately 2-7 cm in diameter in general, and does not show early recurrence after chemotherapy or chemoradiotherapy. There is no report in the literature yet of primary sacral DLBCL with MYC translocation, and this is the first case report. On the other hand, 35 cases of CD10-negative DLBCL with MYC translocation, including the present one, have been reported, and a review of the reported cases showed that the disease predominantly affects Asians, middle-aged or elderly men, shows positivity for either BCL6 or MUM1 and negativity for EBV, and has a high international prognostic index and poor prognosis.     

Sequential development of diffuse large B-cell lymphoma in a patient with angioimmunoblastic T-cell lymphoma

Lymphoma of different histologic type can occur in the same patient. Here, we describe a 64-year-old male patient with angioimmunoblastic T-cell lymphoma (AITL) who subsequently developed diffuse large B-cell lymphoma (DLBCL). At the time of initial diagnosis, histologic examination of a left inguinal lymph node of the patient and a monoclonal pattern of TCRβ gene rearrangement showed typical features of AITL, and there was no evidence of a monoclonal B-cell population. Twenty-six months later, he had generalized lymphadenopathy and organs involvement by DLBCL. A monoclonal IgH gene rearrangement proved de novo development of secondary B-cell lymphoma and excluded relapse of a primary composite lymphoma. The in situ hybridization analysis showed Epstein-Barr-encoded RNA (EBER) sporadic positivity in sample collected from AITL but extensive positivity in the immunoblasts collected from DLBCL. Our observation supports the hypothesis that Epstein-Barr virus (EBV) is etiologically related to AITL in this case. Clonal expansion of EBV-associated DLBCL is a secondary event in AITL via EBV infection or reactivation.     

弥漫大B细胞淋巴瘤免疫表型分型与预后的关系

目的 探讨弥漫大B细胞淋巴瘤（DLBCL）的免疫表型之生发中心B细胞样（GCB）和非GCB两个亚型的特征及其与DLBCL预后的关系。方法 根据肿瘤细胞免疫组织化学EnVision法标记CD10、bc1-6、MUM-1的表达情况,将133例DLBCL分为GCB和非GCB两个亚型。对以下指标的5年总生存率（OS）及5年无进展生存率（PFS）进行了比较：（1）CD10、bc1-6和MUM-1的阳性和阴性病例;（2）GCB亚型与非GCB亚型;（3）不同国际预后指数（IPI）分组中GCB亚型与非GCB亚型的关系。结果 133例DLBCL中,44例（33．1％）CD10阳性,48例（34．6％）bc1-6阳性,60例（45．1％）MUM-1阳性。CD10阳性DLBCL患者的5年OS及PFS均明显高于CD10阴性患者（P=0．041和0．031）;bc1-6阳性DLBCL患者的PFS明显高于bc1-6阴性患者（P=0．044）,MUM．1阳性DLBCL患者的5年0s及PFS均明显低于MUM-1阴性患者（P=0．031和0．028）。GCB型54例（40．6％）,非GCB型79例（59．4％）。GCB型5年OS及PFS均明显高于非GCB型（P=0．004和0．003）。国际预后指数（IPI）0-1分组及2-5分组中,GCB型5年OS及PFS均明显高于非GCB型（IP10-1分组P=0．019和0．014,2-5分组P=0．006和0．009）,其中IPI2-5分组中的非GCB预后最差。结论 DLBCL亚型及其与IPI联合分析可以作为预测患者预后的有效指标。     

Variability in immunophenotype in diffuse large B-cell lymphoma and its clinical relevance

Diffuse large B-cell lymphoma (DLBCL), the single largest category of lymphoma, is a clinically and biologically heterogeneous disease entity. Clinically, patients differ in their mode of presentation and respond variably to therapy. A combination of clinical parameters can be used to predict the patient's response to therapy and survival. The pathological variability of DLBCL is expressed in morphology, immunophenotype, cytogenetic and molecular genetic features. Numerous markers detectable by immunohistochemistry and linked to different aspects of tumour biology have been studied in DLBCL, including lineage-associated and immune markers, proliferation and apoptosis markers, cell adhesion molecules, and more recently stage-specific markers of B-cell differentiation. This review summarizes these studies in regard to their clinical significance and in the light of recent advances in our understanding of the molecular pathology and histogenesis of DLBCL.     

Expression of c-FLIP is primarily detected in diffuse large B-cell lymphoma and Hodgkin's lymphoma and correlates with lack of caspase 8 activation

AIMS: Inhibition of apoptosis is important in the pathogenesis of lymphomas. c-FLIP, a regulator of caspase 8-mediated apoptosis, plays an important role in protecting normal B and T cells from apoptosis and possibly also in lymphomas. Because of contradictory reports about immunohistochemical detection of c-FLIP expression, the aim was to test the specificity of four antibodies in c-FLIP-transfected cells and subsequently to investigate expression of c-FLIP in different types of lymphoma. METHODS AND RESULTS: Two of four antibodies were specific. In primary lymphomas c-FLIP expression was restricted to Hodgkin's lymphomas (> 90%) and diffuse large B-cell lymphomas (44%). Burkitt lymphomas and indolent B-cell lymphomas were negative in all cases. No expression was detected in primary T-cell lymphomas, although expression was observed in one relapsed ALK+ anaplastic large cell lymphoma. Expression of c-FLIP was inversely correlated with caspase 8 activation. CONCLUSIONS: c-FLIP is important in escape of B cells from apoptosis during normal follicle centre cell reaction and may thus be an important early event in the development of B-cell-derived lymphomas. Moreover, non-specific staining of frequently used antibodies might explain discrepancies in different reports of c-FLIP expression.     

Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells

We conducted a trial testing a CD20-specific CAR coupled with CD137 and the CD3ζ moiety in patients with chemotherapy refractory advanced diffuse large B cell lymphomas (DLBCL). Seven patients were enrolled. One of the two patients with no bulky tumor obtained a 14-month durable and ongoing complete remission by cell infusion only, and another attained a 6-month tumor regression. Four of five patients with bulky tumor burden were evaluable for clinical efficacy, three of which attained 3- to 6-month tumor regression. Delayed toxicities related to cell infusion are directly correlated to tumor burden and tumor-harboring sites, and mainly included cytokine release symptoms, tumor lysis symptoms, massive hemorrhage of the alimentary tract and aggressive intrapulmonary inflammation surrounding extranodal lesions. These results show firstly that anti-CD20 CART cells can cause prolonged tumor regression in combination with debulking conditioning regimens for advanced DLBCL. This study is registered at www.clinicaltrials.gov as NCT01735604.     

Nodular lymphocyte predominant Hodgkin lymphoma and diffuse large B-cell lymphoma: a study of six cases concurrently involving the same site

Cotta C V, Coleman J F, Li S & Hsi E D
(2011) Histopathology  59 , 1194–1203
Nodular lymphocyte predominant Hodgkin lymphoma and diffuse large B‐cell lymphoma: a study of six cases concurrently involving the same site Aims: Nodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL) is a slowly progressing neoplasm with a favourable prognosis. However, in a minority of cases (3–12%) it progresses to a clonally related diffuse large B‐cell lymphoma (DLBCL), diagnosed between 6 months and 24 years after NLPHL. This study investigated six cases of NLPHL and DLBCL at the same location. Methods and results: The patients were five men and one woman. In four cases, the site was an axillary lymph node, and in two it was inguinal. In all cases, NLPHL areas had typical morphological and immunophenotypic features. DLBCL involvement was multifocal, diffuse, and characterized by large centroblastic and anaplastic cells. Immunohistochemical studies showed DLBCL cells to be positive for CD20, CD45, and BCL6. In one case, DLBCL cells were positive for BCL2, and in two cases they were positive for MUM‐1. There were no networks of follicular dendritic cells (FDC) associated with DLBCL. Rosettes of PD‐1‐positive and CD57‐positive cells surrounding malignant cells in NLPHL were absent in DLBCL. All the cases were negative for Epstein–Barr virus. No translocations involving MYC were identified in DLBCL. Treatment and outcome were known in four cases. All of these patients were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP), and this was followed by clinical remission (CR). Conclusions: In adequately sampled tumors, DLBCL can be associated with NLPHL at diagnosis. Diffuse architecture, loss of FDC networks, sometimes immunophenotype shift are characteristics of DLBCL associated with NLPHL. Treatment with R‐CHOP usually leads to CR.     

弥漫大B细胞淋巴瘤中miR-339-5 p的表达及意义

目的：检测miR-339-5p在弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma, DLBCL)中的表达,探讨miR-339-5p表达与DLBCL临床病理特征的关系。方法采用显色原位杂交技术检测123例 DLBCL 和20例淋巴结反应性增生( reactive lymphoid hyperplasia, RH)组织中miR-339-5p的表达,并采用免疫组化EnVision两步法检测DLBCL组织中Ki-67和BCL-6蛋白的表达,分析miR-339-5p与BCL-6表达的相关性及二者表达与DLBCL临床病理特征的关系。结果 DLBCL组织中miR-339-5p的阳性率(39．8%,49/123)显著低于RH组织(90．0%,18/20)。活化的B细胞型(ABC型)DLBCL组织中miR-339-5p阳性率(31．0%,22/71)明显低于生发中心的次级B细胞型(GCB型)(51．9%,27/52)。 miR-339-5p在DLBCL中表达降低与Ann Arbor分期晚以及国际预后指数IPI评分高有关(P均<0．05)。 ABC型、GCB型DLBCL中miR-339-5p阴性患者生存率均明显低于miR-339-5p阳性患者(P均<0．01)。 DLBCL中miR-339-5p与BCL-6蛋白表达呈显著负相关(P<0．01)。结论miR-339-5p低表达可能与DLBCL进展和预后不良相关。     

Expression and significance of leptin receptor,p-STAT3 and p-AKT in diffuse large B-cell lymphoma

We investigated the expression and clinical significance of leptin receptor (OBR), p-STAT3 and p-AKT in patients with diffuse large B-cell lymphoma (DLBCL) by immunohistochemical analysis. Immunohistochemistry revealed high expression of OBR, p-STAT3 and p-AKT in 45.0% (36/80), 28.8% (23/80) and 18.8% (15/80) cases of DLBCL, respectively, and minimal staining in 100% (20/20) cases of RLH (P < 0.05). Compared with GCB group, the non-GCB group had higher p-STAT3 expression rate (21/57 vs. 2/23, P < 0.01). The expression of OBR was positively related with that of p-STAT3 and p-AKT in DLBCL patients (P < 0.05). Our data suggest that OBR stimulates the JAK/STAT and PI3K/AKT signaling pathway and induces the phosphorylation of STAT3 and AKT. This may be involved in carcinogenesis and prognosis of DLBCL. The specific inhibitions could interfere in the combination of leptin with OBR and obstruct the JAK/STAT and PI3K/AKT signaling pathways, which could lead to new research and treatment strategies for DLBCL treatment.     

T-cell/histiocyte-rich large B-cell lymphoma associated with a near-tetraploid karyotype and complex genetic abnormalities

Cytogenetic data for T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) are scarcely available. We report here a case of THRLBCL with a near-tetraploid karyotype and complex chromosomal aberrations, without rearrangement of BCL2 or BCL6, and characterized pathologically by a variegated morphologic appearance with areas resembling nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL).     

弥漫大B细胞淋巴瘤中miR-5585-3p的表达及其意义

目的探讨miR-5585-3p在弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中的表达与临床病理特征的相关性及其预后意义。方法选取12例DLBCL石蜡标本进行基因芯片扫描,依据fold change≥1.5、P≤0.05筛选出差异性表达的miRNAs,miR-5585-3p是其中之一。采用qRT-PCR检测95例DLBCL石蜡标本中miR-5585-3p的表达,15例淋巴结反应性增生组织作为对照,并结合患者临床病理学资料进行分析。结果 miR-5585-3p在DLBCL中的表达量显著高于淋巴结反应性增生组织(P0.001),且non-GCB亚型miR-5585-3p的表达水平是GCB型的2.4倍(P=0.006)。miR-5585-3p高表达与淋巴瘤国际预后指数(IPI)呈正相关(P=0.005)。Kaplan-Meier生存分析显示:DLBCL中高表达miR-5585-3p的患者生存率明显低于miR-5585-3p低表达者(P=0.049)。预后多因素Cox分析显示,年龄60岁(P=0.010)、IPI评分3~5分(P=0.004)、高表达miR-5585-3p(P=0.014)为DLBCL独立不良预后指标。结论 miR-5585-3p高表达可能与DLBCL不良预后有关。     

Germinal center B-cell-like diffuse large B-cell lymphoma of the duodenum is associated with t(14;18) translocation

Diffuse large B-cell lymphoma (DLBCL) rarely involves the duodenum, and its clinicopathological characteristics have not been well elucidated. We performed clinicopathological examinations and identified 15 patients with duodenal DLBCL using 18 gastric or colonic DLBCL as a control. Eleven of the 15 patients (73%) were subclassified by immunohistochemical analysis according to the Choi algorithm as germinal center B-cell-like (GCB) type, whereas the 18 control gastric and colonic DLBCL were predominantly subclassified as activated B-cell-like (ABC) type. The classifications according to organ involvement were statistically significant (P= 0.011 and P= 0.035). Macroscopically, the GCB lesions were varied, while all ABC lesions were ulcerative. Fluorescence in situ hybridization analysis revealed a higher frequency of t(14;18) translocation in patients with duodenal DLBCL (3 of 13) as compared with non-duodenal gastrointestinal tract DLBCL (0 of 18), however, the difference was not significant (P = 0.064). Furthermore, the three patients with t(14;18) translocations were classified as GCB. In addition, overall survival of patients was statistically different between those with and without t(14;18) translocation (P= 0.040). In conclusion, duodenal DLBCL predominantly exhibits GCB-type tumors and the frequency of t(14;18) translocation appears to be higher in duodenal GCB-type DLBCL compared to non-duodenal tumors.     

Tumour-associated macrophages in diffuse large B-cell lymphoma: a study of the Osaka Lymphoma Study Group

Wada N, Zaki M A A, Hori Y, Hashimoto K, Tsukaguchi M, Tatsumi Y, Ishikawa J, Tominaga N, Sakoda H, Take H, Tsudo M, Kuwayama M, Morii E & Aozasa K
(2012) Histopathology  60, 313–319
Tumour‐associated macrophages in diffuse large B‐cell lymphoma: a study of the Osaka Lymphoma Study Group Aims: To evaluate the role of tumour‐associated macrophages (TAMs) of the M1 and M2 types in the behaviour of diffuse large B‐cell lymphoma (DLBCL). Methods and results: Double immunohistochemical staining of HLA‐DR/CD68 (M1) or CD163/CD68 (M2) was performed in 101 cases of DLBCL. CD68+ cells represent the total number of TAMs. The average number of double‐positive cells was counted, and the cut‐off value was set at the mean number of counts, i.e. 30.7 and 27.0 for M1 TAMs and M2 TAMs, respectively. That for total TAMs was set at the 90th percentile number of total counts, i.e. 132.3. Cases were categorized into three pairs: high (34 cases) and low (67 cases) M1 TAM groups, high (39 cases) and low (62 cases) M2 TAM groups, and high (10 cases) and low (91 cases) total TAM groups. The difference in overall survival rates was statistically significant between the high and low M2 TAM groups (P < 0.01) and between the high and low total TAM groups (P < 0.05). Multivariate analysis revealed that the presence of a bulky mass and a higher number of M2 TAMs were significant factors for poor prognosis (P < 0.05). Conclusions: Estimation of specific type of macrophages, of the M1 and M2 types, is superior to the estimation of TAMs as a whole (CD68+ cells) for prediction of the prognosis of DLBCL patients.     

microRNA-92a在弥漫大B细胞淋巴瘤患者中的表达及可能机制

目的分析miR-92a在弥漫大B细胞淋巴瘤(DLBCL)患者中的表达与临床病理特征的关系,观察miR-92a对弥漫大B淋巴瘤细胞系OCI-LY10增殖、侵袭能力的影响。方法采用实时荧光定量PCR方法检测86例DLBCL患者肿瘤组织和22例正常淋巴结组织中miR-92a的表达,分析miR-92a表达水平与患者临床病理特征的关系。对弥漫大B淋巴瘤细胞系OCI-LYl0进行miR-92a反义核苷酸(ASO)转染并培养,MTT法检测细胞增殖能力,Transwell小室检测细胞侵袭能力,real-time PCR方法与Western blot方法检测细转染miR-92a ASO后各组细胞KLF4的m RNA和蛋白的表达。结果DLBCL患者淋巴结组织中miR-92a表达水平显著高于对照组(P0.05)。miR-92a在DLBCL患者中的表达与疾病分期显著相关(P0.05),但与患者年龄、性别无关(P0.05)。与对照组相比,miR-92a ASO组OCI-LYl0细胞的增殖侵袭能力明显降低,KLF4蛋白与m RNA表达水平显著升高(P0.05)。结论miR-92a在DLBCL中表达上调,其促进OCI-LY10细胞增殖侵袭的作用机制可能与下调KLF4蛋白表达有关。     

The role of gender in patients with diffuse large B cell lymphoma treated with rituximab-containing regimens: a meta-analysis

Introduction

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL). Although gender has not been included in prognostic systems, male gender has been found as a bad prognostic indicator in Hodgkin lymphoma, follicular lymphoma and chronic lymphocytic leukemia. The relationship between gender and prognosis is not clear in patients with DLBCL treated with rituximab-containing regimens. The aim of this meta-analysis is to determine the prognostic/predictive role of gender in patients with DLBCL treated with rituximab-containing regimens.

Material and methods

We systematically searched for studies investigating the relationships between gender and prognosis in DLBCL treated with rituximab-containing regimens. After careful review, survival data were extracted from eligible studies. A meta-analysis was performed to generate combined hazard ratios for overall survival, disease-free survival (DFS) and event-free survival (EFS).

Results

A total of 5635 patients from 20 studies were included in the analysis. Our results showed that male gender was associated with poor prognosis in terms of overall survival (OS) (hazard ratio (HR) = 1.155; 95% confidence interval (CI): 1.037–1.286; p < 0.009). The pooled hazard ratio for DFS and EFS showed that male gender was not statistically significant (HR = 1.219; 95% CI: 0.782–1.899; p = 0.382, HR = 0.809; 95% CI: 0.577–1.133; p = 0.217).

Conclusions

The present meta-analysis indicated male gender to be associated with a poor prognosis in patients with DLBCL treated with rituximab-containing regimens.     

Activation of MET signaling by HDAC6 offers a rationale for a novel ricolinostat and crizotinib combinatorial therapeutic strategy in diffuse large B‐cell lymphoma

Some histone deacetylases (HDACs) promote tumor cell growth and pan‐ or selective HDAC inhibitors are active in some cancers; however, the pivotal HDAC enzyme and its functions in human diffuse large B‐cell lymphoma (DLBCL) remain largely unknown. Using NanoString nCounter assays, we profiled HDAC mRNA expression and identified HDAC6 as an upregulated HDAC family member in DLBCL tissue samples. We then found that HDAC6 plays an oncogenic role in DLBCL, as evidenced by its promotion of cell proliferation in vitro and tumor xenograft growth in vivo. Mechanistically, the interaction between HDAC6 and HR23B downregulated HR23B expression, thereby reducing the levels of casitas B‐lineage lymphoma (c‐Cbl), an E3 ubiquitin ligase for hepatocyte growth factor receptor (MET), which resulted in the inhibition of MET ubiquitination‐dependent degradation. In addition, enhanced HDAC6 expression and decreased HR23B expression were correlated with poor overall survival rates among patients with DLBCL. Taken together, these results establish an HDAC6–HR23B–MET axis and indicate that HDAC6 is a potent promoter of lymphomagenesis in DLBCL. Thus, a therapeutic strategy based on HDAC6 inhibitors in combination with MET inhibitors is promising. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Sclerosing encapsulating peritonitis (abdominal cocoon) associated with liver cirrhosis and diffuse large B-cell lymphoma: Autopsy case

A case of sclerosing encapsulating peritonitis (SEP) associated with liver cirrhosis (LC) and complicated by diffuse large B-cell lymphoma (DLBCL) is reported herein. A 49-year-old Japanese man had undergone peritoneo-venous shunt against refractory ascites due to hepatitis C virus-positive uncompensated LC for 2 years. After he received a diagnosis of DLBCL of the left neck lymph node 3 months before his death, palliative care was given because of his poor general condition. He developed severe abdominal distention and pain over 1 week and was found to have marked ascites and whole bowel lumped together on abdominal CT. At autopsy, the peritoneum was covered with a thick white membrane and the bowel could not be distinguished, which was macroscopically characterized by a cocoon-like appearance. Histology indicated a proliferation of diffusely thickened or hyalinized fibrocollagenous tissue in the entire peritoneum with a slight chronic inflammatory infiltrate and without remarkable change of mucosa. A diagnosis of SEP, also known as abdominal cocoon, was established based on these features. Additionally, in the abdominal cavity, a large amount of serous ascites and multiple peritoneal nodules or masses involved by DLBCL were recognized. To the authors' knowledge this is the first case report of SEP associated with LC and complicated by the invasion of DLBCL in the abdominal cavity.     

Extranodal diffuse large B cell lymphoma of cutaneous follicle centre lymphoma type: a study of 24 patients with non-cutaneous primary limited stage extranodal diffuse large B cell lymphoma in support of a new concept

Aigner F, Korol D, Schmitt A M & Kurrer M O
(2012) Histopathology  60, 774–784 Extranodal diffuse large B cell lymphoma of cutaneous follicle centre lymphoma type: a study of 24 patients with non‐cutaneous primary limited stage extranodal diffuse large B cell lymphoma in support of a new concept Aims: Follicle centre cell lymphoma of small cell type showing either a follicular or diffuse growth pattern similar to cutaneous follicle centre lymphoma (cFCL) has been recognized in extranodal non‐cutaneous sites. Our aim was (i) to investigate whether diffuse large B cell lymphoma (DLBCL) of cFCL type could be identified in extranodal non‐cutaneous sites and (ii) whether clinical characteristics similar to primary cFCL could be recognized. Methods and results: Of 24 extranodal non‐cutaneous DLBCLs, nine (38%) had large centrocytoid morphology and 15 (62%) were either ‘centrocytoid and centroblastic’ or ‘centroblastic and immunoblastic’. Six centrocytoid cases were Irf‐4 negative, Bcl‐6 positive and at most weakly CD10‐ or Bcl‐2‐positive by immunohistochemistry, consistent with DLBCL of cFCL type. All patients with cFCL type were stage IE and were significantly younger than other patients. Recurrences occurred in two patients and were exclusively extranodal. Conclusion: Our results suggest that DLBCL of cFCL type can be identified in extranodal non‐cutaneous sites and shows clinical characteristics similar to genuine cFCL. We propose to expand the concept of cFCL to encompass large cell lymphomas in extranodal sites.