Terminal Deoxynucleotidyl Transferase Commonly Expresses in Germ Cell Tumors: Evaluation on a Large Series from Multiple Centers

Figures & data

Table 1 TdT Immunoreactivity in GCTs and Sex Cord-Stromal Tumors

Tumor	No. of Cases	Extent of Reactivity* No. (%)					Intensity of Reactivity No. (%)
		0	1+	2+	3+	4+	Mild	Moderate	Strong
SE	95	0 (0)	0 (0)	3 (3)	8 (8)	84 (88)	25 (26)	14 (15)	56 (59)
GCNIS/GCNIS in SE	41	0 (0)	0 (0)	0 (0)	6 (15)	35 (85)	7 (17)	5 (12)	29 (71)
DG	16	1 (6)	0 (0)	1 (6)	2 (13)	12 (75)	4 (27)	4 (27)	7 (47)
EC	4	0 (0)	0 (0)	0 (0)	1 (25)	3 (75)	1 (25)	3 (75)	0 (0)
EG	11	0 (0)	0 (0)	0 (0)	0 (0)	11 (100)	0 (0)	0 (0)	11 (100)
YST	28	28 (100)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
ST	1	1 (100)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
MGCT	23
Components of
SE	13	1 (8)	0 (0)	0 (0)	2 (17)	10 (75)	3 (27)	3 (27)	7 (45)
GCNIS	11	1 (0)	0 (0)	0 (0)	0 (0)	10 (91%)	1 (10)	4 (40)	5 (50)
DG	2	0 (0)	0 (0)	0 (0)	1 (50)	1 (50)	1 (50)	0 (0)	1 (50)
EC	11	0 (0)	0 (0)	0 (0)	2 (18)	9 (82)	5 (45)	1 (9)	5 (45)
YST	10	10 (100)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Teratoma	4	4 (100)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Trophoblast	6	6 (100)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Teratoma	15	15 (100)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
SCST	21	21 (100)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)

Notes: *0, no staining; 1+, fewer than 30 positive; 2+, 31% to 60% positive; 3+, 61–90% positive; 4, more than 90% positive.

Abbreviations: DG, dysgerminoma; EC, embryonal carcinoma; EG, extragonadal germinoma; GCNIS, germ cell neoplasias in situ; MGCT, mixed germ cell tumor; SCST, sex cord-stromal tumor; SE, seminoma; ST, spermatocytic tumor; YST, yolk sac tumor.

Table 2 TdT Immunoreactivity in GCTs in the Most Recent 3 Years

Tumor	No. of Cases	Extent of Reactivity* No. (%)					Intensity of Reactivity
		0	1+	2+	3+	4+	Mild	Moderate	Strong
SE	50	0 (0)	0 (0)	0 (0)	1 (2)	48 (98)	1 (2)	1 (2)	48 (96)
GCNIS or GCNIS in SE	26	1 (0)	0 (0)	0 (0)	0 (0)	25 (96)	0 (0)	0 (0)	25 (100)
DG	8	0 (0)	0 (0)	0 (0)	1 (13)	7 (88)	1 (13)	0 (0)	7 (88)
EC	4	0 (0)	0 (0)	0 (0)	1 (25)	3 (75)	1 (25)	3 (75)	0 (0)
EG	9	0 (0)	0 (0)	0 (0)	0 (0)	9 (100)	0 (0)	0 (0)	9 (100)
MGCT	11
Components of
SE	9	0 (0)	0 (0)	0 (0)	1 (11)	8 (89)	0 (0)	1 (11)	8 (89)
GCNIS	4	0 (0)	0 (0)	0 (0)	0 (0)	4 (100)	0 (0)	0 (0)	4 (100)
DG	9	0 (0)	0 (0)	0 (0)	0 (0)	9 (100)	0 (0)	1 (11)	8 (89)
EC	7	0 (0)	0 (0)	0 (0)	1 (14)	6 (86)	2 (29)	0 (0)	5 (71)

Notes: *0, no staining; 1+, fewer than 30 positive; 2+, 31% to 60% positive; 3+, 61–90% positive; 4, more than 90% positive.

Abbreviations: DG, dysgerminoma; EC, embryonal carcinoma; EG, extragonadal germinoma; GCNIS, germ cell neoplasias in situ; MGCT, mixed germ cell tumor; SE, seminoma.

Table 3 Comparation of TdT Staining to That of PLAP, OCT4, SALL4, CD117, D2-40 in GCTs (Chi-Square/Fisher Exact Test)

Component	TdT Positive	PLAP Positive		OCT4 Positive		SALL4 Positive		CD117 Positive		D2-40 Positive
		No.(%)	P	No.(%)	P	No.(%)	P	No.(%)	P	No.(%)	P
SE (N=108)	107 (99)	105 (97)	0.614	105 (97)	0.614	105 (97)	0.614	104 (96)	0.365	107 (99)	1.00
GCNIS (N=52)	52 (100)	52 (100)	1.00	51 (98)	1.00	52 (100)	1.00	50 (100)	1.00	52 (100)	1.00
DG (N=18)	17 (94)	17 (94)	1.00	18 (100)	1.00	18 (100)	1.00	17 (94)	1.00	18 (100)	1.00
EC (N=15)	15 (100)	13 (87)	0.483	15 (100)	1.00	15 (100)	1.00	2 (13)	0.000	8 (53)	0.006
EG (N=11)	10 (100)	10 (100)	1.00	10 (100)	1.00	10 (100)	1.00	10 (100)	1.00	10 (100)	1.00
YST (N=38)	0 (0)	12 (33)	0.000	0 (0)	1.00	38 (100)	0.000	18 (38)	0.000	0 (0)	1.00

Abbreviations: DG, dysgerminoma; EC, embryonal carcinoma; EG, extragonadal germinoma; GCNIS, germ cell neoplasias in situ; SE, seminoma; YST, yolk sac tumor.

Figure 1 Immunohistochemical staining of TdT in seminomas. Seminomas are characterized by diffuse sheets or nests of tumor cells separated with lymphocytic infiltration; tumor cells have relatively uniform and large nuclei, prominent nucleoli, and abundant clear or eosinophilic cytoplasm (A). Tumor cells were diffusely and strongly positive for TdT (B) and confirmed by OCT4 (C). Old archived tissues may lose TdT antigen to varying degrees and therefore give a misinterpretation of “negative” staining for TdT (D, highlighted between the black arrowheads) (amplification: 10×20, bar=50μm).

Figure 2 Immunohistochemical staining in GCNIS. GCNIS features large atypical tumor cells located (arrow) on the periphery of seminiferous tubules with prominent nucleoli and abundant clear cytoplasm (A). The tumor cells were strongly positive for TdT (B). These GCNIS cells are confirmed by OCT4 (C) (amplification: 10×20, bar=50μm).

Figure 3 Immunohistochemical staining in dysgerminoma. Dysgerminoma presents with sheets of relatively uniform tumor cells with intervening thin fibrous septa and small lymphocytes (A). The tumor cells were diffusely and strongly positive for TdT (B) and confirmed by OCT4 (C) (amplification: 10×10, bar=50μm).

Figure 4 Immunohistochemical staining in EC. ECs demonstrate heterogeneous growth patterns, including solid, complex glandular, or papillary figurations (A). Positivity for TdT in EC (B). The tumors were confirmed by OCT4 (C) (amplification: 10×20, bar=50μm).

Figure 5 Extragonadal germinomas involving the sellar (A1), mediastinal (B1), and right cervical (C1) regions were obtained through core biopsies. The morphologic features are identical to the testicular or ovarian counterpart; crush artifact and fibrous changes (B1) are not uncommon. All of these tumors express TdT (A2–C2) (amplification: 10×20, bar=50μm).