Clinicopathological features of 49 primary gastrointestinal diffuse large B‐cell lymphoma cases; comparison with location, cell‐of‐origin, and frequency of MYD88 L265P

Nagakita, Keina; Takata, Katsuyoshi; Taniguchi, Kohei; Miyata‐Takata, Tomoko; Sato, Yasuharu; Tari, Akira; Ohnishi, Nobuhiko; Noujima-Harada, Mai; Omote, Shizuma; Nakamura, Naoya; Iwamuro, Masaya; Maeda, Yoshinobu; Okada, Hiroyuki; Tanimoto, Mitsune; Yoshino, Tadashi

doi:10.1111/pin.12439

Cited by 24 publications

(26 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Twenty-nine studies have reported that the frequency of MYD88 L265P mutation in 2285 DLBCL patients except for central nervous system (CNS) and testicular lymphomas was 16.5% (95% CI: 11.9–22.6%) 2, 3, 6, 7, 9–11, 13, 16–22, 24, 25, 27, 28, 30, 31, 33–39, 41 . Thirteen 4, 5, 8, 9, 12, 14, 15, 18, 21, 23, 26, 32, 40 and four 8, 9, 21, 29 studies reported the prevalence of MYD88 L265P mutation in 378 CNS and 88 testicular DLBCL patients.…”

Section: Resultsmentioning

confidence: 99%

“…Eighteen studies reported that MYD88 L265P mutation was detected in 255 (21%) of 1236 activated B-cell-like (ABC) or non-germinal center B-cell-like (non-GCB) subtype and in 44 (6%) of 766 GCB subtype patients 2, 6, 7, 9, 11, 16, 18, 21, 24, 25, 27, 30, 34, 36–39, 41 . The MYD88 L265P mutation was significantly associated with ABC or non-GCB subtype (OR = 3.414; 95% CI: 2.243–5.195; p < 0.001, Q = 19.986, I 2 = 14.865) (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Clinicopathologic significance of MYD88 L265P mutation in diffuse large B-cell lymphoma: a meta-analysis

Lee

Jeong

Choi

et al. 2017

Sci Rep

View full text Add to dashboard Cite

The precise clinicopathologic significance of myeloid differentiation primary response gene (MYD88) L265P mutation in diffuse large B-cell lymphomas (DLBCLs) remains elusive. To investigate the frequency and clinicopathologic significance of the MYD88 L265P mutation in DLBCLs, we conducted a meta-analysis of 40 published studies on 2736 DLBCL patients. We collected relevant published research findings identified using the PubMed and Embase databases. The effect sizes of outcome parameters were calculated using a random-effects model. In this meta-analysis, the MYD88 L265P mutation in DLBCL showed a significant difference according to tumor sites. The overall incidence of the MYD88 L265P mutation in DLBCLs, excluding the central nervous system and testicular DLBCLs, was 16.5%. Notably, the MYD88 L265P mutation rates of CNS and testicular DLBCL patients were 60% and 77%, respectively. Interestingly, the MYD88 L265P mutation was more frequently detected in activated B-cell-like (ABC) or non-germinal center B-cell-like (GCB) than GCB subtype (OR = 3.414, p < 0.001). The MYD88 L265P mutation was significantly associated with old age and poor overall survival, but not with sex and clinical stage. This pooled analysis demonstrates that the MYD88 L265P mutation is significantly associated with the tumor sites and molecular subtypes in DLBCL patients.Myeloid differentiation primary response gene (MYD88) is an adaptor protein that activates the nuclear transcription factor κB (NF-κB) signaling through most of the Toll-like receptors (TLRs) 1 . An L265P mutation, a change from leucine (CTC) to proline (CCG), in the MYD88 Toll/interleukin (IL)-1 receptor domain, recruits MYD88 protien to the cytoplasmic tail of TLRs to form an active complex. The complex promotes NF-κB and Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) signaling 1 .Recently, many investigators have reported that the prevalence of MYD88 L265P mutation ranges from 0% to 94% in different series of diffuse large B-cell lymphoma (DLBCL) patients 2-41 . However, since the MYD88 L265P mutation occurs at various frequencies of DLBCL, a general consensus on clinicopathologic implications has not been reached. DLBCL is a heterogeneous non-Hodgkin's lymphoma mainly comprising molecular subtypes such as germinal center B-cell-like (GCB) and activated B-cell-like (ABC) types 42 . Several studies have suggested that the frequency of MYD88 L265P mutation may vary depending on the tumor site or molecular subtype of DLBCL 2,8,21,24,30,41 , but individual studies with different designs hinder clear conclusions. Furthermore, the clinicopathologic significance of the MYD88 L265P mutation in each DLBCL patient was controversial.To address these controversies, we conducted a meta-analysis to examine the frequency of MYD88 L265P mutation and the relationship between this mutation and the clinicopathologic parameters of DLBCL patients. ResultsPrevalence of MYD88 L265P mutation in diffuse large B-cell lymphoma. On pooled analysis of 40 studies, includin...

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Clinicopathologic significance of MYD88 L265P mutation in diffuse large B-cell lymphoma: a meta-analysis

Lee

Jeong

Choi

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In one analysis, 33% of GI lymphomas were non-GCB, whereas MYD88 or CD79B mutations were identified in only <5% [86]. In an examination of 49 cases from Japan, the non-GCB phenotype was seen in 50%, but MYD88 mutation only in 6% [87]. Another series examining genetic profiles of GI DLBCL found only 3% rate of EZH2 Y641 mutation and 17% rate of BCL2 rearrangements in the GCB subgroup (none in the ABC subgroup), suggesting a low prevalence of the EZB genotype [88, 18].…”

Section: Prognosis Of Extranodal Dlbcl Arising From Specific Anatomicmentioning

confidence: 99%

Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence

Ollila

Olszewski

2018

Curr. Treat. Options in Oncol.

115

107

View full text Add to dashboard Cite

Diffuse large B cell lymphoma (DLBCL) arises from extranodal organs in about 30% of cases. Its prognosis and risk of recurrence in the central nervous system (CNS) vary according to the primary site of origin. Recent studies begin to clarify these differences using molecular classification. Testicular, breast, and uterine DLBCL (as well as possibly primary cutaneous DLBCL, leg-type) share a high prevalence of the non-germinal center B cell (non-GCB) phenotype and the MYD88/CD79B-mutated (MCD) genotype. These biologic features, which resemble primary CNS lymphoma, may underlie their stage-independent propensity for CNS involvement. Management of these lymphomas should involve CNS prophylaxis, preferably using systemic high-dose methotrexate to prevent intraparenchymal recurrence. Involvement of the kidneys, adrenal glands, ovary, bone marrow, lung, or pleura usually indicates disseminated disease, conferring worse prognosis. Involvement of these sites is often associated with high CNS-International Prognostic Index (IPI), concurrent MYC and BCL2 or BCL6 rearrangements, or intravascular lymphoma-risk factors warranting CNS prophylaxis. In contrast, craniofacial, thyroid, localized bone, or gastric lymphomas have a variable prevalence of the non-GCB phenotype and lack MYD88 mutations. Their outcomes with standard immunochemotherapy are excellent, and the risk of CNS recurrence is low. We recommend individualized consideration of CNS prophylaxis based on the CNS-IPI score and anatomical proximity in cases of epidural, orbital, or skull involvement. Rituximab-containing immunochemotherapy is a standard approach for all extranodal DLBCLs. Surgery is no longer required for any primary site, but routine consolidative radiation therapy is recommended for testicular lymphoma. Radiation therapy also appears to be associated with better progression-free survival in primary bone DLBCL. Future studies should better distinguish primary from secondary sites of extranodal involvement, and investigate the association of newly identified genotypes with the risk of CNS or systemic recurrence.

show abstract

“…Primary gastrointestinal DLBL generally expresses pan B-cell markers, such as CD19, CD20, CD22, CD79a, occasionally MUM-1+, and bcl-2+, and 50%-75% of cases express surface or cytoplasmic immunoglobulins [20,21]. In a study of 49 primary gastrointestinal DLBL cases, the histology and immunophenotyping showed that CD20+ and CD3-were the markers in all the cases [22]. On average, the Ki-67 labeling index was 68.3% (range, 35%-90%) and CD10 was positive in 44.9% of the cases, CD5 was positive in 4.1% of the cases, and c-MYC was positive in 23.4% of the cases [22].…”

Section: Discussionmentioning

confidence: 99%

Clinical outcomes of surgical management for primary gastrointestinal diffuse large B-cell lymphoma: At a single institution experience

Jang

Lim

Kuk

et al. 2017

Korean J Clin Oncol

View full text Add to dashboard Cite

The study aimed to analyze peri/postoperative outcomes and long-term oncologic outcomes after surgical management for primary gastrointestinal diffuse large B-cell lymphoma (DLBL). Methods: Between January 2001 and December 2013, 19 patients who underwent surgery for primary gastrointestinal DLBL were retrieved from a retrospective database. Results: With a median follow up of 49.2 months, the most common tumor locations were the terminal ileum and cecum (n=14, 73.7%) and stomach (n=4, 21.1%). The most common clinical symptoms were abdominal pain (n=15, 78.9%) and intussusceptions (n=5, 26.3%). None of the patients had B symptoms. Emergency surgery was undertaken in 36.8% (n=7) of the patients. Mean mass size was 8.4 cm; 4 patients (21.1%) had a bulky mass (>10 cm). The International Prognostic Index (IPI) scores were low (n=11, 57.9%), low-intermittent (n=7, 36.8%), and high-intermittent (n=1, 5.3%). Patients` staging was IE (n=9, 47.4%), IIE (n=8, 42.1%), and IVE (n=2, 10.5%) based on the Ann Arbor staging system, and I (n=2, 10.5%), II1 (n=5, 26.4%), IIE (n=10, 52.6%), and IV (n=2, 10.5%) based on the Lugano staging system. B-lymphocyte antigen CD20 was positive in most patients (n=17, 89.5%) and Ki-67 was high (>70%) in 12 patients (63.2%). Two types of chemotherapy were administered: cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisolone (n=5, 26.3%), rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisolone (n=13, 68.4%). The 5-year disease-free survival rate was 94.4% and the 5-year overall survival rate was 89.5%. Conclusion: Surgery for primary gastrointestinal DLBL is feasible and acceptable. Low staging of primary gastrointestinal DLBL has good prognosis.

show abstract

Clinicopathological features of 49 primary gastrointestinal diffuse large B‐cell lymphoma cases; comparison with location, cell‐of‐origin, and frequency of MYD88 L265P

Cited by 24 publications

References 21 publications

Clinicopathologic significance of MYD88 L265P mutation in diffuse large B-cell lymphoma: a meta-analysis

Clinicopathologic significance of MYD88 L265P mutation in diffuse large B-cell lymphoma: a meta-analysis

Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence

Clinical outcomes of surgical management for primary gastrointestinal diffuse large B-cell lymphoma: At a single institution experience

Contact Info

Product

Resources

About