|
|
|
|
Germinal Center-Derived Diffuse Large B-cell Lymphomas with Aberrant Co-expression of MUM1 in Adults and Children
Lei Chen1, Jianbo Shuai2, Tingting Liu3*
1Department of Pathology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. 2Department of Pathology, Baoshan People's Hospital, Baoshan city, Yunnan province, China. 3Department of Pediatric Hematology/Oncology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Abstract
The aim of this study is to analyze the clinical and pathological features of germinal center (GC)-derived diffuse large B-cell lymphomas (DLBCL) with aberrant co-expression of MUM1 and to further analyze the differences between adults and pediatric populations. Clinical and pathological data of 32 cases of GC-derived DLBCL with aberrant co-expression of MUM1 were reviewed and analyzed. Thirty-two cases were categorized into pediatric (n=12) and adult (n=20) groups. GC-derived DLBCL with aberrant co-expression of MUM1 was found to manifest a wide age range, extensive involvement sites, different histopathological distribution, and complex clinical presentations. Compared to adults, pediatric patients showed a significantly higher frequency of Waldeyer's ring (WR) involvement (P=0.008), higher frequency of stage II (P=0.035), and lower incidence of fatality (P=0.014). Among the 32 cases, lymphomas were frequently involved in WR, followed by the gastrointestinal tract, lymph nodes, and bone marrow. Pediatric patients showed a significantly higher frequency of WR involvement than adult patients (P=0.008). Lymphomas involving WR in adults showed similar localized clinical stages, excellent outcomes, and pathological features compared to the disease in the pediatric population. Lymphomas involving the gastrointestinal tract in adults shared clinical features with the disease in children but with high P53 positive expression. GC-derived DLBCL with aberrant co-expression of MUM1 in adults is clinically more heterogeneous than children. Tumors involving WR in adults share many similarities to their pediatric counterparts.
Keywords: GC-derived DLBCL, MUM1, Germinal center, Adults, Children
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. DLBCL is classified into germinal center B cell (GCB)-like DLBCL, and the activated B cell (ABC)-like DLBCL, according to the immunoreactions of CD10, BCL6, and interferon regulatory factor 4 (IRF4)/multiple myeloma oncogene 1 (MUM1);[1] however, ~15% remains unclassified.[2] Substantially, according to the Hans algorithm, IRF4/MUM1 is considered a non-GC marker, whereas CD10 and BCL6 are considered GC markers. Notably, IRF4/MUM1 and GC markers show mutually exclusive expression patterns in B-cells, suggesting a reciprocal regulation of IRF4/MUM1 and GC markers expression.[3]
GCB and ABC markers have been the most favored algorithms to predict prognosis in DLBCL patients.[4] Previous studies showed that the ABC type was an independent predictor of progression-free survival and overall survival, whereas the GCB type was not a prognostic factor.[5] Although MUM1 is used as a post-GC marker, IRF4/MUM1 positive expression is observed in a small proportion of GC B-cells that reside within the light zone of GCs and displays the morphology of centrocytes, or plasmablastic features in some cases.[6] In a previous study, although MUM1 is used as a post-GC marker, DLBCL with coexpression of CD10 and MUM1 was classified as a GCB subtype. MUM1 expression is associated with worse outcomes in CD10+ DLBCL patients.[7] However, it is still unclear whether all DLBCLs with coexpression of CD10, BCL6, and MUM1 represent clinically and pathologically the same disease with poor prognosis.
About one-third of DLBCLs manifest primarily in extranodal sites.[8] Waldeyer’s ring (WR) represents one of the most common extranodal sites.[9] WR DLBCLs display distinct clinicopathologic features compared with conventional DLBCLs and seem to be associated with a better outcome
Our study was approved by the Ethics Committee of Xinhua Hospital, Affiliated with Shanghai Jiaotong University School of Medicine. From September 2014 to January 2020, 643 cases of lymphoma were obtained from a single institution of Shanghai Xinhua Hospital. According to histopathological, and immunohistochemical analyses, 32 cases diagnosed as DLBCL aberrantly co-expressing CD10, BCL6, and MUM1/IRF4 in >50% of tumor cells were included in the study.[11]
Ann Arbor classification and the International pediatric NHL staging system were staged for adult and pediatric patients, respectively. Clinical information was recorded for each patient, including age, gender, date of initial diagnosis, symptoms and signs at presentation, clinical stage, and follow-up information.
Pediatric patients received chemotherapy from the China Children's Cancer Group (CCCG)-BNHL protocol. Regimens of R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone), R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and adriamycin) or EPOCH, both R-CHOP and R-EPOCH, R-CHOP and MTX (methotrexate), R-MA (methotrexate and cytarabine), both R-CHOP and ICE (Ifosfamide, carboplatin, and etoposide), and R-COP (rituximab, cyclophosphamide, vincristine, and prednisone), were used for adult patients.
The morphologic and immunophenotypic features were studied on formalin-fixed and paraffin-embedded tissue sections of the diagnostic biopsies. Immunohistochemistry was performed using a panel of monoclonal and polyclonal antibodies, as follows: CD10 (clone 56C6, Leica Biosystems); BCL6 (clone P1F6, DAKO); MUM1 (clone MUM1p, DAKO); Ki-67 (clone MIB-1, DAKO); BCL2 (clone 100/D5, DAKO); MYC (DAKO); P53 (clone DO-7, DAKO). MYC was considered as positive when greater than 40% of tumor cells exhibited staining.[12] A positive threshold was defined at 50% for BCL2 and MUM1, 30% for CD10 and BCL6. GCB phenotype was evaluated by antibodies of C10, BCL6, and MUM1.
Contingency tables were analyzed using Pearson Chi-square statistic. Differences with P-value <0.05 were defined as statistically significant. The software of SPSS version 17.0 (SPSS Inc., Chicago, IL, USA) was used for statistical calculations.
Results and Discussion
Table 1. Clinical features of germinal center-derived B-cell lymphomas with IRF4/MUM1 positive expression in 32 cases |
||||||||
|
Age (year)/ Gender |
Clinical initial diagnosis |
Site of Involvements |
LDH (u/L) |
Stage |
Treatment protocol |
Follow-up (months) |
||
|
EN |
LN |
|||||||
|
Pediatric patients |
||||||||
|
1 |
5/M |
Tongue base mass |
Tongue base |
Cervical LN |
233 |
II R2 |
CCCG-BNHL |
CR (21) |
|
2 |
5/M |
Parotid gland mass |
Parotid gland |
Cervical LN |
220 |
II R2 |
CCCG-BNHL |
CR (14) |
|
3 |
6/M |
Intussusception |
Ileum |
Mesenteric LN |
243 |
II R1 |
CCCG-BNHL |
CR (30) |
|
4 |
7/M |
Tonsillitis |
Palatine tonsil |
None |
191 |
II R2 |
CCCG-BNHL |
CR (58) |
|
5 |
8/M |
Tonsillitis |
Palatine tonsil |
Cervical LN |
280 |
II R2 |
CCCG-BNHL |
CR (32) |
|
6 |
8/M |
Intussusception |
Ileocecum |
Mesenteric LN, bone marrow |
306 |
IV R4 |
CCCG-BNHL |
CR (41) |
|
7 |
10/F |
Abdominal mass |
Mesenteric LN |
349 |
III R3 |
CCCG-BNHL |
CR (52) |
|
|
8 |
10/M |
Tonsillitis |
Nasopharynx and tongue base |
Mesenteric LN |
242 |
III R3 |
CCCG-BNHL |
CR (28) |
|
9 |
11/M |
Pharyngeal mass |
Palatine tonsil, nasopharynx |
None |
179 |
I |
CCCG-BNHL |
CR (50) |
|
10 |
11/M |
Cervical mass |
Palatine tonsil |
Cervical LN |
213 |
II |
R-CHOP |
CR (41) |
|
11 |
13/M |
Intussusception |
None |
167 |
II |
NA |
NA |
|
|
12 |
17/M |
Parotid gland mass |
Nasopharynx and parotid gland |
Cervical LN |
204 |
II |
R-CHOP |
CR (25) |
|
Adult patients |
||||||||
|
33/M |
Cervical mass |
Spleen |
Cervical LN |
320 |
III |
R-CHOP |
CR (22) |
|
|
14 |
38/M |
Abdominal mass |
None |
Multiple LN |
915 |
III |
Resection |
DOD (0) |
|
15 |
49/F |
Intussusception |
Ascending colon, bone marrow |
Mesenteric LN |
NA |
IV |
Resection |
DOD (2) |
|
16 |
54/M |
Tonsillitis and cervical mass |
palatine tonsil |
Cervical LN |
258 |
II |
R-EPOCH |
CR (30) |
|
17 |
56/M |
Abdominal mass |
Stomach, liver, pancreas, bone marrow |
None |
1135 |
IV |
R-CHOP+HD-MTX |
CR (24) |
|
18 |
56/M |
Cervical mass |
Palatine tonsil |
Cervical LN |
126 |
II |
R-CHOP |
CR (52) |
|
19 |
58/M |
Axillary mass |
None |
Multiple LN |
246 |
III |
R-EPOCH |
CR (57) |
|
20 |
59/M |
Pancreatic mass |
Pancreas, duodenum |
Multiple LN |
851 |
IV |
R-EPOCH |
DOD (1) |
|
21 |
60/F |
Cervical mass |
Palatine tonsil, nasopharynx, uterus |
Multiple LN |
284 |
IV |
R-EPOCH |
CR (24) |
|
22 |
65/M |
Inguinal mass |
None |
Inguinal LN |
NA |
I |
Resection |
CR (47) |
|
23 |
66/M |
Lumbar vertebra mass |
Lumbar vertebra, kidney, bone marrow |
No |
343 |
IV |
R-EPOCH |
CR (26) |
|
24 |
67/F |
Pancreatic mass |
Pancreas, gallbladder |
No |
NA |
III |
R-CHOP |
DOD (4) |
|
25 |
67/M |
Gastric mass |
Stomach |
Mesenteric LN |
817 |
II |
R-CHOP |
CR (44) |
|
26 |
67/M |
Bowel obstruction |
Colon |
Retroperitoneal LN |
NA |
II |
NA |
NA |
|
27 |
68/F |
None |
Temporal lobe |
None |
184 |
I |
R-MA |
CR (15) |
|
28 |
72/M |
Brain mass |
Multiple intracranial masses, bone marrow |
None |
223 |
IV |
Biopsy |
DOD (6) |
|
29 |
75/F |
Gastric mass |
Stomach |
NA |
NA |
NA |
NA |
NA |
|
30 |
84/M |
Tonsillitis and cervical lymphadenopathy |
Palatine tonsil |
Cervical and axillary LN |
314 |
II |
R-CHOP |
DOD (6) |
|
31 |
85/F |
Cervical mass |
No |
Cervical LN |
NA |
NA |
NA |
NA |
|
32 |
86/M |
Abdominal mass Bladder cancer |
Ileocecum |
Retroperitoneal and mediastinal LN |
164 |
IV |
R-CHOP+ R-EPOCH |
DOD (24) |
CR, complete remission; DLBCL, diffuse large B-cell lymphoma; DOD, died of disease; F, female; LN, lymph node; Lt., left; M, male; NA, not available; R-CHOP, (R, Rituximab; CHOP, cyclophosphamide, adriamycin, vincristine, prednisone); R-EPOCH regimen (R, Rituximab; EPOCH, etoposide, prednisone, vincristine, cyclophosphamide, and adriamycin).
Clinical information is summarized in Table 1. A total of 32 cases were included in the study, ranging from 5 to 86 years, with a median of 55 years. There were 12 pediatric patients with a median age of 9 years (range, 5–17 years), and 20 adult patients with with a median age of 65.5 years (range, 33–86 years). The pediatric group included 6 cases of (< 10 years) and 6 cases within the (10–< 20 years) groups of age, while adults had 0, 2, 1, 5, 7, and 5 cases from the groups of (20–< 30 year), (30–< 40 year), (40–< 50 year), (50–< 60 year), (60–< 70 year), and (≥
70 years) of age, respectively, of the 32 cases, 25 were males, and 7 were females.
Four patients (13%) had a nodal presentation, whereas 28 patients (87%) showed an extra-nodal presentation. Twelve cases involved the Waldeyer's ring, 10 cases involved the gastrointestinal tract, 4 cases involved bone marrow, 1 case involved the central neural system, and 1 case involved the retroperitoneum and pelvis. The 12 pediatric patients were exclusively involved in extra-nodal sites (12/12, 100%), including WR, gastrointestinal tract (GIT), and retroperitoneum and pelvis in 8, 3, and 1 case, respectively. Adult patients' tumor involvements were distributed differently in lymph nodes (4/20, 20%) and extra-nodal sites (16/20, 80%). Pediatric patients showed a significantly higher frequency of Waldeyer's ring involvement than adult patients (8/12, 67% vs. 4/20, 20%, P=0.008), and a lower frequency of nodal and bone marrow than adult patients (Table 2).
Table 2. Comparisons of clinical, histological subtypes, and immunohistochemical features between pediatric and adult patients |
||||
|
|
Pediatric patients n = 12 |
Adult patients n = 20 |
Total patients n = 32 |
P-value (P vs. A) |
|
Clinical features |
|
|
|
|
|
Median age, year (range) |
9 (5-17) |
65.5 (33-86) |
55 (5-86) |
|
|
M: F |
11:1 |
14:6 |
25:7 |
0.151 |
|
Involvement sites |
|
|
|
|
|
Lymph nodes |
0/12 |
4/20 |
4/32 |
0.098 |
|
WR |
8/12 |
4/20 |
12/32 |
0.008 |
|
GIT |
3/12 |
7/20 |
10/32 |
0.555 |
|
Multiple sites and bone marrow |
0/12 |
4/20 |
4/32 |
0.098 |
|
Elevated serum LDH level |
6/12 |
11/14 |
17/26 |
0.127 |
|
Clinical stage |
|
|
|
|
|
Stage I |
1/12 |
2/18 |
3/30 |
0.804 |
|
Stage II |
8/12 |
5/18 |
13/30 |
0.035 |
|
Stage III |
2/12 |
4/18 |
6/30 |
0.709 |
|
Stage IV |
1/12 |
7/18 |
8/30 |
0.064 |
|
Outcome |
|
|
|
|
|
CR/NR |
11/11 |
10/17 |
21/28 |
0.014 |
|
DOD |
0/11 |
7/17 |
7/28 |
|
|
Immunohistochemical features |
|
|
|
|
|
BCL2+ expression |
8/12 |
13/20 |
21/32 |
0.923 |
|
P53+ expression |
4/12 |
10/20 |
14/32 |
0.358 |
|
MYC+ expression |
3/12 |
6/20 |
9/32 |
0.761 |
Symptoms were closely related to the location and size of the masses. The 12 cases involving WR frequently presented with mass pharyngeal discomfort and tonsillitis. The 10 cases involving the gastrointestinal tract mostly presented with abdominal pain, in which 4 cases were initially diagnosed with intussusception. Serum LDH level was elevated in 17 patients.
Symptoms were closely related to the location and size of the masses. The 12 cases involving WR frequently presented with mass pharyngeal discomfort and tonsillitis. The 10 cases involving the gastrointestinal tract mostly presented with abdominal pain, in which 4 cases were initially diagnosed with intussusception. Serum LDH level was elevated in 17 patients.
Of the 30 patients with available clinical information, clinical stages of I, II, III, and IV were shown in 3, 13, 6, and 8 cases. Clinical stages of I, II, III, and IV were identified in 1, 8, 1, and 1 case among children, respectively, and in 2, 5, 4, and 7 cases, respectively, among the adults. Pediatric patients showed a significantly higher frequency of stage II than adult patients (8/12, 67% vs. 5/18, 28%, P=0.035).
Treatment data was available in 28 cases, including 4 patients with surgical resection/biopsy, and 24 with surgical resection/biopsy and post-chemotherapy. Twenty-one patients were alive at follow-up, with a median follow-up of 41 months (range 14-58 months). Seven adults passed away due to multiple organ failure after resection in 3 cases and 4 during chemotherapy. Compared to pediatric cases, adult cases showed a higher incidence of fatality (0/11, 0% vs. 7/17, 41.2%, P=0.014).
All cases showed expression of CD10, BCL6, and MUM1/IRF4 in more than 50% of tumor cells. Among the 32 cases, MYC was positive in 11 cases. BCL2 was positive in 21 cases. P53 showed positive expression in 14 cases.
Table 3. Clinicopathological features among the Waldeyer's ring, gastrointestinal, and lymph node involvements of GC-derived B-cell lymphomas with MUM1 positive expression |
||||
|
Variable |
WR (n=12) |
GIT (n=10) |
||
|
P (n=8) |
A (n=4) |
P (n=3) |
A (n=7) |
|
|
Median age, y (range) |
11 (5-17) |
60 (54-84) |
13 (6-13) |
67 (34-86) |
|
Clinical features |
|
|
|
|
|
M: F |
8: 0 |
3:1 |
3:0 |
4:3 |
|
Clinical stage |
|
|
|
|
|
Localized stage of I/II |
7/8 |
3/4 |
2/3 |
2/7 |
|
Advanced stage of III/ IV |
1/8 |
1/4 |
1/3 |
5/7 |
|
Immunohistochemical features |
|
|
|
|
|
BCL2+ expression |
5/8 |
2/4 |
2/3 |
6/7 |
|
P53+ expression |
3/8 |
3/4 |
0/3 |
5/7 |
|
MYC+ expression |
2/8 |
1/4 |
1/3 |
1/7 |
|
Outcome |
|
|
|
|
|
CR/NR |
12/12 |
3/4 |
3/3 |
3/7 |
|
DOD |
0/12 |
1/4 |
0/3 |
4/7 |
CR, complete remission; DOD, died of disease; F, female; M, male; WR, Waldeyer's ring; GIT, gastrointestinal tract.
As shown in Table 3, 12 cases involving WR were identified, with a median age of 56 years age (range 5-84 years). They predominantly occurred in males (M: F =11: 1). Tumors commonly involved in palatine tonsil, palatine tonsil with nasopharynx, tongue base, and nasopharynx and tongue base. Ten cases involving WR exhibited localized clinical stage I/II, including 7 children and 3 adult patients, while two cases presented with advanced stage III/ IV. Only 1 case passed away, and the other 11 cases achieved complete remission without relapse.
The 10 cases involving GIT were included, with ages ranging from 6 to 86 years. Tumors are commonly localized in the ileocecum, stomach, colon, ileum, pancreas, duodenum, stomach, and colon. Patients presented with localized clinical and advanced stages in 4 and 6 cases, respectively. Compared to pediatric patients, adult patients presented with a significantly higher frequency of P53 positive expression (5/7 vs. 0/3, P=0.038) and a slightly higher fatality rate.
The 4 four cases involving multiple sites and bone marrow predominantly occurred in adults aged 49, 56, 66, and 72 years old. Patients presented with clinical stage IV; two died of multiple organ failure.
In the present study, we characterized the clinical and pathological features of 32 cases of GC-derived DLBCL with aberrant co-expression of MUM1. These cases present with a bimodal age distribution, male predominance, various clinical stages, high frequency of BCL2 positive expression, and moderate expression of MYC and P53.
Age is a well-established prognostic impact of lymphoma and children have a more favorable outcome than adults.[13] In our study, patients of GC-derived DLBCL with aberrant co-expression of MUM1 mostly occurred in children and adults > 50 years of age. An important question is whether adults represent the same disease as children. The comparison result demonstrated that although pediatric and adult cases shared the similar clinical and pathological features, adult cases showed higher tumor location complexity and higher incidence of fatality, highlighting the genetic and phenotypic heterogeneity in adults. Recent studies have shown that DLBCL with aberrant coexpression of CD10+BCL6+MUM1+ in adult cases showed higher genetic complexity and higher mutational load with frequent MYD88 and KMT2D mutations.[14]
The primary site of lymphoma, including extra-nodal and nodal territories, was proposed as a criterion for separating groups. Adult DLBCLs, although belonging to the same group, showed clinical alterations associated with involving sites. DLBCL involving WR displayed peculiar clinicopathologic features compared to nodal counterpart, with usually localized stage disease, low rate of BCL2 rearrangements, and better outcome.[10] Accordingly, in this study, the WR group predominantly presented with localized stage with excellent response to conventional chemotherapy. Nevertheless, within the adult group, clinicopathologic features were similar to the pediatric counterpart, indicating that these cases might have similar molecular characteristics.
The gastrointestinal tract is the most common extranodal site of lymphoma, and there is no significant difference between GC and ABC groups.[15] In our study, the GIT group showed both localized and advanced stages. Adult patients showed a slightly higher rate of advanced stage and incidence of fatality than children. High positive expression of P53 was shown in adult cases involving GIT. Therefore, it was predicted to be different molecular features that may impact therapeutic strategies.
Previous work has shown the unfavorable prognosis determined by a concordant marrow infiltration, with lower progression-free survival and overall survival.[12] BM infiltration represents a subset with a poor prognosis, whereas the prognostic impact of discordant BM infiltration could be limited to ABC cases.[16] In our study, a disease involving multiple sites and bone marrow occurred in patients older than 40, predominantly presents with advanced stage and poor prognosis, indicating that these cases had molecular features similar to ABC cases and different from other DLBCL involving WR and GIT.
IRF4 translocation is identified in a small subset of GC-derived B-cell lymphomas, including GCB-type DLBCL.[17] We reported as IRF4/MUM1 positive lymphoma to be referred to as the new entity of large B-cell lymphoma with IRF4 rearrangement (LBCL-IRF4).[18] LBCL-IRF4 is newly named in WHO classification and shows mostly a GCB phenotype but with strong MUM1/IRF4 expression.[19] DLBCL-IRF4 in adults showed a different molecular profile when compared with LBCL-IRF4 in the pediatric population, suggesting that MUM1/IRF4 plays an important role in the different phenotypes of DLBCL.[14]
In conclusion, we have demonstrated that IRF4/MUM1 positive expression was related to wide age distribution, extensive involvement sites, and different clinicopathological subtypes in germinal center-derived B-cell lymphomas. Furthermore, DLBCL-IRF4 in adults is similar to its pediatric counterpart, especially in patients involving WR. Our data suggests that within the group of IRF4-rearranged cases in adults, there are important differences from its pediatric counterpart.
None.
None.
This work was supported by the Shanghai Municipal Commission of Health and Family Planning (201840165) and the National Natural Science Foundation of China (82000193).
This study was approved by the ethics committee of Xin Hua Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine.
All patients enrolled provided written informed consent.
1. Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103(1):275-82.
2. Wright G, Tan B, Rosenwald A, Hurt EH, Wiestner A, Staudt LM. A gene expression-based method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proc Natl Acad Sci USA. 2003;100(17):9991-6.
3. De Silva NS, Simonetti G, Heise N, Klein U. The diverse roles of IRF4 in late germinal center B-cell differentiation. Immunol Rev. 2012;247(1):73-92.
4. Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie RD, Delabie O, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103(1):275-82.
5. Irawan C, Iskandar M, Harahap AS, Rumende CM, Ham MF. MUM1 Expression versus Hans Algorithm to Predict Prognosis in Indonesian Diffuse Large B-Cell Lymphoma Patients Receiving R-CHOP. Cancer Manag Res. 2022;14(1):925-35.
6. Falini B, Fizzotti M, Pucciarini A, Bigerna B, Marafioti T, Gambacorta M, et al. A monoclonal antibody (MUM1p) detects expression of the MUM1/IRF4 protein in a subset of germinal center B cells, plasma cells, and activated T cells. Blood. 2000;95(6):2084-92.
7. Lu TX, Miao Y, Wu JZ, Gong QX, Liang JH, Wang Z, et al. The distinct clinical features and prognosis of the CD10⁺MUM1⁺ and CD10⁻Bcl6⁻MUM1⁻ diffuse large B-cell lymphoma. Sci Rep. 2016;6(1):20465.
8. d'Amore F, Christensen BE, Brincker H, Pedersen NT, Thorling K, Hastrup J, et al. Clinicopathological features and prognostic factors in extranodal non-Hodgkin lymphomas. Danish LYFO Study Group. Eur J Cancer. 1991;27(10):1201-8.
9. Vega F, Lin P, Medeiros LJ. Extranodal lymphomas of the head and neck. Ann Diagn Pathol. 2005;9(6):340-50.
10. de Leval L, Bonnet C, Copie-Bergman C, Seidel L, Baia M, Brière J, et al. Diffuse large B-cell lymphoma of Waldeyer's ring has distinct clinicopathologic features: a GELA study. Ann Oncol. 2012;23(12):3143-51.
11. Miles RR, Raphael M, McCarthy K, Wotherspoon A, Lones MA, Terrier‐Lacombe MJ, et al. Pediatric diffuse large B-cell lymphoma demonstrates a high proliferation index, frequent c-Myc protein expression, and a high incidence of germinal center subtype: Report of the French-American-British (FAB) international study group. Pediatr Blood Cancer. 2008;51(3):369-74.
12. Frauenfeld L, Castrejon-de-Anta N, Ramis-Zaldivar JE, Streich S, Salmerón-Villalobos J, Otto F, et al. Diffuse large B-cell lymphomas in adults with aberrant coexpression of CD10, BCL6, and MUM1 are enriched in IRF4 rearrangements. Blood Adv. 2022;6(7):2361-72.
13. Mitchell KA, Finn WG, Owens SR. Differences in germinal center and non-germinal center phenotype in gastric and intestinal diffuse large B-cell lymphomas. Leuk Lymphoma. 2008;49(9):1717-23.
14. Chigrinova E, Mian M, Scandurra M, Greiner TC, Chan WC, Vose JM, et al. Diffuse large B-cell lymphoma with concordant bone marrow involvement has peculiar genomic profile and poor clinical outcome. Hematol Oncol. 2011;29(1):38-41.
15. Alonso-Álvarez S, Alcoceba M, García-Álvarez M, Blanco O, Rodríguez M, Baile M, et al. Biological Features and Prognostic Impact of Bone Marrow Infiltration in Patients with Diffuse Large B-cell Lymphoma. Cancers (Basel). 2020;12(2):474.
16. Liu Q, Salaverria I, Pittaluga S, Jegalian AG, Xi L, Siebert R, et al. Follicular lymphomas in children and young adults: a comparison of the pediatric variant with usual follicular lymphoma. Am J Surg Pathol. 2013;37(3):333-43.
17. Chen L, Al‐Kzayer LA, Liu T, Kobayashi N, Nakazawa Y, Koike K. IFR4/MUM1-positive lymphoma in Waldeyer ring with co-expression of CD5 and CD10. Pediatr Blood Cancer. 2017;64(2):311-4.
18. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-405.
19. Mohamed AA, Obaid NE, Abdelghani S, Alfahed A, Waggiallah HA, Eltayeb LB. Immunohistochemical expression of survivin and Ki-67 as tumor markers in breast cancer infected females: a cross-sectional study. Pharmacophore. 2020;10(5):41-5.
|
||||||||
