Fig. 1Morphologic features of tumor sproutings. Tumor sprouting is present in the lower portion of the figure (blue box) separated from the main tumor in the upper portion (A) and a magnified view of blue-boxed area shows tumor sprouting. Tumor sprouting exhibits typical nuclear features of papillary thyroid carcinoma, but lacks evidence of lymphatic emboli such as an endothelialized tumor cluster or endothelialized lymphatic spaces (B). Another example of tumor sprouting. Tumor sprouting is easily found with cytokeratin 19 (CK19) or high molecular weight cytokeratin (HMW-CK) staining. Immunoreactivity with D2-40 is not observed (C, hematoxylin and eosin staining; D, CK19 staining; E, HMW-CK staining; F, D2-40 staining). (G) Another example of tumor sprouting (blue box). Tumor sproutings are observed around the main tumor mass. (H) High magnification view of tumor sprouting.
Fig. 2Microscopic figures of separate tumor clusters excluded from tumor sprouting and figures of lymphovascular tumor emboli. Tumor clusters too close to the tumor border or desmoplastic area (arrows) are excluded from tumor sproutings (A, hematoxylin and eosin [H&E] staining; B, cytokeratin 19 [CK19] staining). (C) Tumor clusters with desmoplastic reactions are also excluded. Lymphovascular tumor emboli (arrows) showing endothelialized lymphatic spaces with D2-40 staining (D, H&E staining; E, CK19 staining; F, D2-40 staining).
Fig. 3Recurrence-free survival analysis of papillary thyroid carcinoma patients. Kaplan-Meier survival plots with tumor multiplicity (A), extrathyroidal extension (B), lymphovascular invasion (C), lymph node metastasis (D), tumor sprouting (E), and resection margin (F) data.
Table 1.Clinicopathologic characteristics of patients
|
Range |
Mean |
No. of patients (%) |
Sex |
- |
- |
|
Male |
|
|
37 (18) |
Female |
|
|
167 (82) |
Age (yr) |
14-79 |
48.07 |
|
≥ 45 |
|
|
122 (60) |
<45 |
|
|
82 (40) |
Tumor size (cm) |
1.1-5.5 |
1.65 |
|
>2 |
|
|
37 (18) |
≤2 |
|
|
167 (82) |
Tumor multiplicity |
1-10 |
1.87 |
|
Present |
|
|
87 (43) |
Absent |
|
|
117 (57) |
Desmoplasiaa
|
0-20 |
3.40 |
|
Present |
|
|
157 (23) |
Absent |
|
|
47 (77) |
Extrathyroidal extension |
- |
- |
|
Present |
|
|
177 (87) |
Absent |
|
|
27 (13) |
Resection margin status |
- |
- |
|
Positive |
|
|
65 (32) |
Negative |
|
|
139 (68) |
Lymph node dissection |
- |
- |
|
Not performed |
|
|
97 (48) |
Performed |
1-75b
|
9.67b
|
107 (52) |
Presence of metastasis |
1-26c
|
5.24c
|
68 (64) |
Absence of metastasis |
|
|
39 (36) |
Tumor sprouting |
|
|
|
Absent |
- |
- |
103 (50) |
Present |
|
|
101 (50) |
Size (cm) |
0.01-0.30 |
0.08 |
|
Distance from main tumor (cm) |
0.1-1.0 |
0.30 |
|
No. of tumor sproutings |
1-20 |
3.52 |
|
Table 2.Tumor sprouting and clinicopathologic characteristics of 204 papillary thyroid carcinoma patients
|
n (%) |
Tumor sprouting
|
LVI
|
LN metastasisa
|
Recurrence
|
|
Present |
p-value |
Present |
p-value |
Present |
p-value |
Present |
p-value |
Sex |
|
|
|
|
|
|
|
|
|
Male |
37 (18) |
22 (59) |
.124 |
5 (14) |
.019 |
18 (49) |
.025 |
3 (8) |
.629 |
Female |
167 (82) |
79 (47) |
|
5 (3) |
|
50 (30) |
|
14 (8) |
|
Age (yr) |
|
|
|
|
|
|
|
|
|
≥ 45 |
122 (60) |
58 (48) |
.294 |
5 (4) |
.369 |
35 (29) |
.059 |
7 (6) |
.085 |
<45 |
82 (40) |
43 (52) |
|
5 (6) |
|
33 (40) |
|
10 (12) |
|
Tumor size (cm) |
|
|
|
|
|
|
|
|
|
>2 |
37 (18) |
18 (49) |
.526 |
4 (11) |
.085 |
21 (57) |
.001 |
3 (8) |
.629 |
≤ 2 |
167 (82) |
83 (50) |
|
6 (4) |
|
47 (28) |
|
14 (8) |
|
Multiplicity |
|
|
|
|
|
|
|
|
|
Present |
87 (43) |
48 (55) |
.105 |
7 (8) |
.072 |
34 (39) |
.088 |
11 (13) |
.049 |
Absent |
117 (57) |
53 (45) |
|
3 (3) |
|
34 (29) |
|
6 (5) |
|
Desmoplasia |
|
|
|
|
|
|
|
|
|
Presentb
|
157 (23) |
76 (48) |
.341 |
9 (6) |
.284 |
53 (34) |
.481 |
14 (9) |
.419 |
Absent |
47 (77) |
25 (53) |
|
1 (2) |
|
15 P2) |
|
3 (6) |
|
ETE |
|
|
|
|
|
|
|
|
|
Present |
177 (87) |
91 (51) |
.118 |
10 (6) |
.234 |
63 (36) |
.059 |
17 (10) |
.080 |
Absent |
27 (13) |
10 (37) |
|
0 (0) |
|
5 (19) |
|
0 (0) |
|
Margin status |
|
|
|
|
|
|
|
|
|
Positive |
65 P2) |
42 (65) |
.002 |
3 (5) |
.600 |
29 (45) |
.015 |
10 (15) |
.016 |
Negative |
139 (68) |
59 (42) |
|
7 (5) |
|
39 (28) |
|
7 (5) |
|
Tumor sprouting |
|
|
|
|
|
|
|
|
|
Present |
101 (50) |
NA |
NA |
10 (10) |
.001 |
56 (56) |
<.001 |
14 (14) |
.004 |
Absent |
103 (50) |
NA |
|
0 (0) |
|
12 (12) |
|
3 (3) |
|
LVI |
|
|
|
|
|
|
|
|
|
Present |
10 (5) |
10 (100) |
.001 |
NA |
NA |
9 (90) |
<.001 |
3 (30) |
.040 |
Absent |
194 (95) |
91 (47) |
|
NA |
|
59 (30) |
|
14 (7) |
|
LN metastasisa
|
|
|
|
|
|
|
|
|
|
Present |
68 (33) |
56 (84) |
<.001 |
9 (13) |
<.001 |
NA |
NA |
12 (18) |
.001 |
Absent |
136 (67) |
45 (33) |
|
1 (1) |
|
NA |
|
5 (4) |
|
Table 3.Tumor sprouting and clinicopathologic characteristics of 107 papillary thyroid carcinoma patients with lymph node dissection
|
n (%) |
Tumor sprouting
|
LVI
|
LN metastasis
|
Recurrence
|
|
Present |
p-value |
Present |
p-value |
Present |
p-value |
Present |
p-value |
Sex |
|
|
|
|
|
|
|
|
|
Male |
22 (21) |
16 (73) |
.148 |
4 (18) |
.084 |
18 (82) |
.037 |
3 (14) |
.527 |
Female |
85 (79) |
49 (58) |
|
5 (6) |
|
50 (59) |
|
10 (12) |
|
Age (yr) |
|
|
|
|
|
|
|
|
|
≥ 45 |
60 (56) |
37 (62) |
.491 |
4 (6.7) |
.348 |
35 (58) |
.143 |
6 (10) |
.317 |
<45 |
47 (44) |
28 (60) |
|
5 (11) |
|
33 (70) |
|
7 (15) |
|
Tumor size (cm) |
|
|
|
|
|
|
|
|
|
>2 |
27 (25) |
18 (67) |
.311 |
4 (15) |
.161 |
21 (78) |
.059 |
3 (11) |
.576 |
≤ 2 |
80 (75) |
47 (58) |
|
5 (6) |
|
47 (59) |
|
10 (13) |
|
Multiplicity |
|
|
|
|
|
|
|
|
|
Present |
54 (50) |
33 (61) |
.548 |
7 (13) |
.085 |
34 (63) |
.529 |
10 (19) |
.039 |
Absent |
53 (50) |
32 (60) |
|
2 (4) |
|
34 (64) |
|
3 (6) |
|
Desmoplasia |
|
|
|
|
|
|
|
|
|
Presenta |
87 (81) |
51 (59) |
.249 |
8 (9) |
.469 |
53 (61) |
.179 |
11 (13) |
.546 |
Absent |
20 (19) |
14 (70) |
|
1 (5) |
|
15 (75) |
|
2 (10) |
|
ETE |
|
|
|
|
|
|
|
|
|
Presenta
|
95 (89) |
60 (63) |
.131 |
9 (10) |
.328 |
63 (66) |
.090 |
13 (14) |
.193 |
Absent |
12 (11) |
5 (42) |
|
0 (0) |
|
5 (42) |
|
0 (0) |
|
Margin status |
|
|
|
|
|
|
|
|
|
Positive |
46 (43) |
28 (61) |
.571 |
2 (4) |
.169 |
29 (63) |
.542 |
7 (15) |
.291 |
Negative |
61 (57) |
37 (61) |
|
7 (12) |
|
39 (64) |
|
6 (10) |
|
Tumor sprouting |
|
|
|
|
|
|
|
|
|
Present |
65 (61) |
NA |
NA |
9 (14) |
.009 |
56 (86) |
<.001 |
10 (15) |
.166 |
Absent |
42 (39) |
NA |
|
0 (0) |
|
12 (29) |
|
3 (7) |
|
LVI |
|
|
|
|
|
|
|
|
|
Present |
9 (8) |
9 (100) |
.009 |
NA |
NA |
9 (100) |
.014 |
3 (33) |
.077 |
Absent |
98 (92) |
56 (58) |
|
NA |
|
59 (60) |
|
10 (10) |
|
LN metastasis |
|
|
|
|
|
|
|
|
|
Present |
68 (64) |
56 (82) |
<.001 |
9 (13) |
.014 |
NA |
NA |
12 (18) |
.017 |
Absent |
39 (36) |
9 (23) |
|
0 (0) |
|
NA |
|
1 (3) |
|
Table 4.Multivariate analysis results of recurrence-free survival
Variable |
Parameter |
p-value |
Hazard ratio |
95% CI |
Lymph node metastasis |
Present vs absent |
.088 |
2.771 |
0.859-8.942 |
Lymphovascular invasion |
Present vs absent |
.291 |
2.047 |
0.542-7.730 |
Tumor multiplicity |
Present vs absent |
.104 |
2.300 |
0.842-6.286 |
Resection margin |
Involved vs uninvolved |
.040 |
2.819 |
1.048-7.583 |
Tumor sprouting |
Present vs absent |
.252 |
2.238 |
0.565-7.730 |