Supplementary Table 1: Summary of the reported 112 ALK+LBCL cases
No. / Author, Year / Case No. / Partner gene / Karyotype* / Age / Sex / Stage / Stage (high/low) / Survival(months) / ALK IHC pattern
1 / Delsol, 1997 / 1 / 47,XY,+12,t(12;12)(p11;q11) / 53 / M / III / high / 22 / GCS
2 / 2 / NA / 15 / M / I / low / 180 / GCS
3 / 3 / NA / 37 / M / III / high / 10 / GCS
4 / 4 / NA / 44 / M / II / low / 20 / GCS
5 / 5 / NA / 67 / F / III / high / 11 / GCS
6 / 6 / CLTC / NA / 51 / M / IV / high / 26 / GCS
7 / 7 / NA / 60 / M / III / high / 9 / non-GCS
8 / Adam, 2003 / - / NPM / 35–48,XY,-1,t(1;14)(q21or23;q32),
t(2;5)(p23;q35),-4,
+der(8),inv(11)(p11p15),
der(11)t(7;11)(q22or31;q21),-11,
der(14)t(1;14)(q21or23;q32),+21 / 35 / M / II / high / 14 / non-GCS
9 / Chikatsu, 2003 / - / CLTC / "Complex abnormality in which chromosome 2 was translocated to chromosome 17" / 36 / F / IV / high / 11 / GCS
10 / De Paepe, 2003 / 1 / CLTC / failed / 10 / M / II / high / 27 / GCS
11 / 2 / CLTC / 46-47,XX,i(1)(q10),
der(2)add(2)(p13)t(2;3)(q37;q21),
der(5)t(3;5)(q25;q34),add(6)(q10),
+der(6)t(6;14)(p21;q11),
+8,del(10)(p12),
?inv(12)(q15q24),-14,add(17)(p11),
add(17)(q15),+19,inc[cp7] / 13 / F / III / high / 3 / GCS
12 / 3 / CLTC / 44-46,XY,-Y,idic(1)(p11),del(2)(p23),
del(5)(q23),+14,add(17)(?q23)[cp5] / 26 / M / II / high / 44 / GCS
13 / Gascoyne, 2003 / 1 / CLTC / t(2;17;7)(p23;q23;q?22) / 46 / M / III / high / 27 / GCS
14 / 2 / CLTC / NA / 45 / F / NA / NA / GCS
15 / 3 / CLTC / NA / 49 / M / IV / high / 12 / GCS
16 / 4 / CLTC / NA / 48 / M / I / high / 29 / GCS
17 / 6 / CLTC / NA / 58 / M / IV / high / 5 / GCS
18 / Onciu, 2003 / 1 / NPM / NA / 16 / M / IV / high / 24 / non-GCS
19 / 2 / NPM / 45,XY,der(1;11)(q10;q10),
t(2;5)(p23;q35)[3]/
46,XY[10] / 10 / M / II / high / 156 / non-GCS
20 / Colomo, 2004 / - / NA / 34 / M / NA / 8 / GCS
21 / McManus, 2004 / - / CLTC / NA / 21 / M / II / high / 24 / GCS
22 / Gesk, 2005 / 1 / CLTC / NA / 13 / M / II / high / NA / GCS
23 / 2 / NA / 12 / F / II / high / 48 / GCS
24 / 3 / NA / 16 / M / IV / high / 12 / GCS
25 / Ishii, 2005 / - / 82<3n>,XY,add(X)(q22),+1,
add(1)(p11)x2,-2,add(2)(p21),+3,-5,
add(5)(q31)x2,+del(6)(q?),+8,
+add(11)(p15),+12,-14,+16,
del(16)(p13)x2,+18,+mar1,
+mar2,+mar3,+mar4x2,+mar5,
+mar6,+mar7[6]/83,idem,
+add(3)(p13),-4,del(6),+7,
t(7;8)(p15;p23),9,-del(16),+17,
add(18)(p11),+21,-mar2,+mar[1]/
81,idem,+add(3)(p11),add(3)(q12),-6,
-15,-del(16),-18,-mar2,-mar5,-mar7,
+5mar[1]/46,XY[4] / 33 / M / I / high / 31 / non-GCS
26 / Rudzki, 2005 / 1 / NA / 48 / M / III / high / 3 / GCS
27 / 2 / NPM / NA / 49 / M / IV / high / NA / non-GCS
28 / Bubala, 2006 / - / CLTC / NA / 9 / M / IV / high / 5 / GCS
29 / Isimbaldi, 2006 / - / CLTC / NA / 9 / F / I / high / 9 / GCS
30 / Reichard, 2007 / 1 / NA / 41 / F / I / high / 58 / GCS
31 / 2 / NA / 49 / F / I / high / 36 / GCS
32 / 3 / NA / 71 / M / IV / high / 22 / GCS
33 / 4 / NA / 53 / M / I / high / GCS
34 / Stachurski, 2007 / - / 87,X,-X,-Y,-Y,+1,add(1)(p13)x2,+6,
add(6)(q12)x2,-8,add(8)(p11.1),-9,
-10,-18,+mar / 33 / M / IV / high / 10 / GCS
35 / Choung, 2008 / 1 / CLTC / 87~89,XXYY,del(1)(p21)x2,
t(2;12)(p14;q24.3),+6,
del(6)(q21)x2,-7,-10,-13,-14,-17,
-17,-17,+2~4mar[cp5]/46,XY[10] / 35 / M / IV / high / 15 / GCS
36 / 2 / CLTC / NA / 24 / M / IV / high / 17 / GCS
37 / Lee, 2008 / 1 / RANBP2 / NA / 26 / F / IV / high / 6 / non-GCS
38 / 2 / NA / 35 / M / IV / high / 18 / GCS
39 / 3 / NA / 24 / M / IV / high / 17 / GCS
40 / Beltran, 2009 / 1 / NA / 27 / M / IV / high / 11 / GCS
41 / 2 / NA / 41 / F / I / high / 13 / GCS
42 / 3 / NA / 13 / F / II / high / 62 / GCS
43 / 4 / NA / 70 / M / III / high / 72 / GCS
44 / Laurent, 2009 / 2 / NA / 14 / M / I / high / 5 / GCS
45 / 5 / NA / 14 / M / I / high / 13 / GCS
46 / 6 / CLTC / NA / 48 / M / IV / high / 10 / GCS
47 / 12 / NA / 29 / M / IV / high / 6 / GCS
48 / 13 / NA / 31 / M / IV / high / 18 / GCS
49 / 15 / NA / 43 / M / II / high / 4 / GCS
50 / 17 / NA / 34 / M / IV / high / 8 / GCS
51 / 18 / NA / 42 / M / II / high / 14 / GCS
52 / 19 / NA / NA / M / II / high / NA / GCS
53 / 20 / NA / 45 / M / NA / NA / NA / GCS
54 / 21 / NA / 29 / F / I / high / NA / GCS
55 / 22 / NA / 56 / M / I / high / 38 / GCS
56 / 24 / NA / 65 / M / I / high / 77 / GCS
57 / 25 / NA / 32 / F / IV / high / 45 / GCS
58 / 26 / NA / 37 / M / I / high / 16 / non-GCS
59 / 27 / NA / 35 / M / IV / high / 13 / GCS
60 / 28 / CLTC / NA / 47 / F / II / high / NA / GCS
61 / 29 / CLTC / NA / 27 / M / IV / high / 19 / GCS
62 / 30 / NA / NA / F / IV / high / 9 / GCS
63 / 31 / CLTC / NA / 85 / M / IV / high / 8 / GCS
64 / 33 / NA / NA / M / NA / NA / NA / GCS
65 / 34 / NA / 57 / M / IV / high / 11 / GCS
66 / 35 / NA / 22 / M / II / high / 24 / GCS
67 / 36 / NA / 45 / M / II / high / 65 / GCS
68 / 37 / NA / 19 / M / IV / high / 18 / GCS
69 / 38 / NA / 47 / M / III / high / 53 / GCS
70 / Momose, 2009 / 1 / CLTC / NA / 53 / M / IV / high / NA / GCS
71 / 2 / CLTC / NA / 41 / M / II / high / 5 / GCS
72 / Li, 2009 / 1 / NA / 57 / M / IV / high / 24 / NA
73 / 2 / NA / 14 / M / I / high / 14 / NA
74 / Zhang, 2009 / - / CLTC / 85-87<±3n>,XXY,i(1)(q10),
add(2)(p23),+3,
dic(3)t(3;7)(p23;q11.2),
+del(4)(q21),+del(5)(q13),
+der(5)t(3;5)(p13;q22),+6,
+del(7)(q11.2),+8,add(9)(q34.1),
t(9;14)(q13;q32),add(11)(p14),
i(11)(q10),der(13;13)(q10;q10),
der(15)t(1;15)(q21;p13),-16,17x2,
+18,+19,+20,+21 / 32 / M / NA / low / 50 / GCS
75 / Bedwell, 2010 / - / SEC31A / 45,XY,der(1;17)(q10;q10),
t(2;4)(p2?4;q21) / 66 / M / IV / high / 0.75 / GCS
76 / Van Roosbroeck, 2010 / 1 / SEC31A / 45-47,XY,+X[5],del(1)(q32),
i(1)(q10)del(2)(q33)[1],
del(6)(q22)[3],+7[2],
der(13)t(3;13)(q25;p13)[7],-14[6]
-15[2],add(16)(p13),add(20)(q13),
+add(20)(q13)[3][cp8]
75-91,idem,add(2)(q25),
der(16)t(1;16)(q21;q24),
+1-3mar[cp4] / 27 / M / I / high / 27 / GCS
77 / 2 / NPM / 43-46,XX,+X,+X[1],
der(1)t(1;17)(q21;q11),
der(2)t(2;2)(p23;q21),
der(2)?inv(2)(p13q21)del(2)(q21),
der(7)t(1;7)(q21;q22),-15[2],
-20[cp3] / 33 / F / IV / high / 19 / non-GCS
78 / Holtan, 2011 / - / CLTC / t(2;17)(p23;q23) / 60 / M / I / high / NA / GCS
79 / Li, 2011 / - / NA / 44 / M / I / high / NA / GCS
80 / Shi, 2011 / - / 76~79,der(X)t(X;2)(q21;p23)x2,-Y,-Y,-1,
dic(1;14)(p36.1;p11.2),del(2)(p23)x2,
del(3)(q27)x2,add(4)(q21),-5,add(5)(p13),
add(6)(q21),del(6)(q21),add(7)(q11.2)x2,
-8,der(8;13)(q10;q10),add(8)(q24)x2,-9,
-10,-11,add(12)(q13),del(12)(p11.2),
der(12)t(2;12)(p23;q24.1),+13,-14,-14,-15,add(15)(p11.2),-17,-17,+19,
add(19)(p13)x2,-22,-22,-22,+1~2mars / 49 / M / II / high / NA / GCS
81 / Takeuchi, 2011 / - / SQSTM1 / t(2;5)(p23.1;q35.3) / 67 / M / NA / NA / NA / non-GCS
82 / Wang, 2011 / - / CLTC / NA / 24 / M / I / high / 72 / GCS
83 / Yin, 2012 / - / NA / 17 / F / III / high / 10 / GCS
84 / Chen, 2013 / - / CLTC / NA / 52 / M / NA / 9 / GCS
85 / d'Amore, 2013 / - / SQSTM1 / NA / 39 / M / >=III / high / 11 / non-GCS
86 / Ishida, 2013 / - / NA / 67 / M / NA / NA / 24 / GCS
87 / Lin, 2013 / 1 / NA / 29 / M / NA / NA / NA / NA
88 / 2 / NA / 62 / M / NA / NA / NA / NA
89 / 3 / NA / 72 / M / NA / NA / NA / NA
90 / Valera, 2013 / 1 / NA / 34 / M / NA / NA / NA / GCS
91 / 2 / NA / 42 / M / NA / NA / NA / GCS
92 / 3 / NA / 30 / M / NA / NA / NA / GCS
93 / 4 / NA / 38 / M / NA / NA / NA / GCS
94 / 5 / NA / 29 / M / NA / NA / NA / GCS
95 / 6 / NA / 28 / M / NA / NA / NA / GCS
96 / 7 / NA / 32 / M / NA / NA / NA / GCS
97 / 8 / NA / 22 / M / NA / NA / NA / GCS
98 / 9 / NA / 38 / M / NA / NA / NA / GCS
99 / 10 / NA / 34 / M / NA / NA / NA / GCS
100 / 11 / NA / NA / F / NA / NA / NA / GCS
101 / 12 / NA / 40 / M / NA / NA / NA / GCS
102 / Nakatsuka, 2014 / - / NA / 67 / M / NA / NA / 33 / GCS
103 / Chapman
-Fredrics, 2014 / - / CLTC / NA / 39 / M / IV / high / 1.5 / GCS
104 / Hashimoto, 2014 / - / SEC31A / NA / 31 / F / IV / high / 24 / GCS
105 / Ritesh, 2014 / NA / 20 / M / IV / high / NA / GCS
106 / Wass, 2014 / - / NA / 27 / F / IV / high / NA / non-GCS
107 / Xing, 2014 / NA / 26 / M / II / high / NA / GCS
108 / Yu, 2015 / 1 / CLTC / NA / 25 / M / I / high / 16 / GCS
109 / 2 / NA / 32 / M / III / high / 8 / GCS
110 / Zanelli, 2015 / - / NA / 53 / M / III / high / 35 / GCS
111 / Li, 2015 / - / CLTC / 46,XX / 21 / M / III / high / 24 / GCS
112 / Lin, 2015
(present case) / 2 / EML4 / NA / 46 / F / IV / high / 3 / non-GCS
GCS, granular cytoplasmic staining; IHC, immunohistochemistry.
* Karyotypes were quoted directly from the original reports.
Supplementary Table 2:
Comparison of clinical characteristics according to ALK IHC pattern in the ALK staining pattern reported 107 ALK+LBCL cases
ALK IHC pattern known cases (N=107)GCS / non-GCS / P-value
Number / 94 / 13 / -
Sex (Male/Female) / 77/17 / 9/4 / 0.28
Age / Median / 35 / 35 / 0.98
Adult/Children / 78/12 / 11/2 / 1
Stage / I to II / 33 / 4 / 0.54
III to IV / 41 / 8
Lesions / Nodal / 41 / 5 / 0.76
Extranodal / 44 / 7
Nodal lesions (Yes/No) / Cervical / 34/21 / 8/2 / 0.47
Axillary / 14/39 / 3/8 / 1
Supraclavicular / 15/40 / 2/9 / 0.71
Mediastinal / 13/40 / 2/8 / 1
Abdominal / 13/47 / 2/8 / 1
Inguinal / 6/53 / 2/8 / 0.33
Retroperitoneal / 12/45 / 2/8 / 1
Extranodal lesions
(Yes/No) / Bone marrow / 14/52 / 0/8 / 0.34
Bone / 7/56 / 2/9 / 0.62
Liver / 8/54 / 1/10 / 1
Gastrointestinal / 9/57 / 2/9 / 0.65
Genital / 2/60 / 0/11 / 1
Soft tissue / 4/59 / 0/11 / 1
Oral/Laryngeal / 3/56 / 1/10 / 0.50
Nasopharyngeal / 6/57 / 1/10 / 1
Central Nervous system / 4/58 / 0/11 / 1
Lung or pleulal / 1/61 / 1/10 / 0.28
Kidney / 1/61 / 0/11 / 1
Spleen / 8/69 / 0/12 / 0.59
LDH / Elevated/Normal / 15/17 / 3/1 / 0.60
B symptoms / Yes/No / 15/11 / 4/2 / 1
Partner gene / Confirmed/Not confirmed / 32/62 / 9/4 / -
Confirmed partner gene
(Number of cases) / CLTC (29),
SEC31A (3) / NPM (5),
SQSTM1 (2), RANBP2 (1),
EML4 (1)
Treatment / CHOP-like/Other / 56/10 / 10/3 / 0.44
Stem cell transplantation / Yes/No / 12/59 / 3/10 / 0.69
IHC, immunohistochemistry; GCS, granular cytoplasmic staining.
Supplementary Table 3:
Immunophenotype of the 64 ALK+LBCL adult cases for which ALK staining pattern and survival time were reported and the comparison according to ALK IHC pattern (Positive/Tested)
ALK IHC pattern and survival time known adult cases (N=64)GCS / non-GCS / P-value
CD19 / 1/5 / 0/2 / 1
CD20 / 3/36 / 0/6 / 1
CD79a / 6/34 / 1/6 / 1
PAX5 / 2/10 / 1/4 / 1
BOB1 / 0/0 / 1/1 / -
OCT2 / 3/3 / 2/2 / -
CD57 / 10/16 / 1/2 / 1
CD38 / 5/8 / 1/2 / 1
CD138 / 28/29 / 2/4 / 0.033
VS38 / 13/13 / 2/2 / -
MUM1 / 12/13 / 2/3 / 0.35
CD15 / 2/9 / 0/1 / 1
CD30 / 6/37 / 2/7 / 0.59
CD10 / 1/4 / 0/1 / 1
BCL6 / 0/4 / 0/1 / -
IgA / 16 / 4 / 1
IgG / 2 / 0
kappa / 7 / 2 / 0.57
lambda / 17 / 2
CD43 / 4/13 / 0/2 / 1
CD45 / 18/22 / 3/4 / 1
EMA / 31/32 / 7/7 / 1
CD2 / 0/7 / 0/3 / -
CD3 / 0/30 / 0/6 / -
CD4 / 21/27 / 2/4 / 0.27
CD5 / 0/10 / 0/4 / -
CD7 / 0/4 / 0/2 / -
CD8 / 0/10 / 0/3 / -
CD56 / 1/11 / 0/2 / 1
TIA1 / 0/7 / 0/2 / -
perforin / 2/2 / 1/2 / 1
EBV / 0/21 / 0/3 / -
HHV8 / 0/8 / 0/1 / -
MIB1 / median 55% / - / -
pSTAT3 / 2/2 / 1/1 / -
BCL2 / 0/6 / 0/0 / -
cytokeratin / 1/12 / 1/2 / 0.28
IHC, immunohistochemistry; GCS, granular cytoplasmic staining.