Clinicopathological features and prognosis assessment of extranodal follicular dendritic cell sarcoma

Table 1 Clinicopathological and therapeutic data of nine new cases of extranodal FDC sarcoma (Cases 1-9)

Case No.	Age (yr)	Gender	Sites	Size (cm)	HG	MC (/10 HPF)	Year of onset	Initial diagnoses	Initial treatment	Recurrence, DFT (mo)	Disease status	Follow-up (mo)
1	60	M	Tonsil	5.0	Low	< 1	2002	Granuloma	Surg + RT		NED	86
2	35	F	Parapharyn-geal space	5.0	High	10	2003	NPC	Surg	LR, 2	DOD	12
3	63	M	Infratem-poral fossa	4.0	Low	1	2003	PNET	Surg + RT + ChT		NED	72
4	30	F	Pyform sinus	5.0	High	9	2004	FDC sarcoma	Surg + RT	DM (lung), 25	DOD	25
5	23	M	Mediastinum	8.0	Low	3	2006	MPNST	Surg + RT + ChT	DM (bone), 45	AWD	45
6	45	M	Liver	14.5	Low	< 1	2007	FDC sarcoma	Surg		NED	27
7	36	F	Mesentery	15.0	High	7	2007	Malignant GIST	Surg	DM (liver, ovary), 4	AWD	27
8	28	F	Parapharyn-geal space	6.0	High	3	2008	FDC sarcoma	Surg + RT + ChT	DM (lung), 14	AWD	22
9	55	M	Tonsil	2.0	High	9	2008	FDC sarcoma	Surg + RT	LR, 18	AWD	21

AWD: Alive with disease; ChT: Chemotherapy; DFT: Disease-free time following operation; DM: Distant metastasis; DOD: Died of disease; GIST: Gastrointestinal stromal tumor; HG: Histological grades; LR: Local recurrence; MC: Mitotic counts; MPNST: Malignant nerve sheath tumor; NED: No evidence of disease; NPC: Nasopharyngeal carcinoma; PNET: Primitive neuroepidermal tumor; RT: Radiotherapy; Surg: Surgery; FDC: Follicular dendritic cell.

Table 2 Primary antibodies and antigen retrieving procedures

Antibodies	Origins and clones	Dilutions	Antigen retrieval	Sources
Pan-cytokeratin	MAb, AE1/AE3	1:80	MW-citrate	Invitrogen
EMA	MAb, Mc5	1:100	MW-citrate	Invitrogen
Vimentin	MAb, V9	1:200	MW-citrate	NeoMarker
Desmin	MAb, ZC18	1:80	MW-citrate	Invitrogen
SMA	MAb, IA4	1:100	Not treated	Invitrogen
CD45	MAb, RP2/18	1:120	MW-citrate	Novacastro
CD68	MAb, KP1	1:200	MW-citrate	Zeta
S-100 protein	PAb, rabbit	1:400	MW-citrate	Dako
CD21	MAb, 2G9	1:20	AC-EDTA	NeoMarker
CD23	MAb, SP23	1:25	MW-citrate	NeoMarker
CD35	MAb, KuN241	1:20	AC-EDTA	NeoMarker
CD1a	MAb, MTB1	1:20	MW-citrate	Zeta
Podoplanin	MAb, D2-40	1:50	AC-EDTA	Zeta
p53 protein	MAb, DO-7	1:100	AC-EDTA	NeoMarker
Ki-67 antigen	MAb, MIB-1	1:200	AC-EDTA	Zymed

Antibody suppliers: Dako, Glostrup, Denmark; Invitrogen Corporation, Carlsbad, CA, USA; NeoMarkers Inc., Fremont, CA, USA; Novacastro Laboratories Ltd., Newcastle upon Tyne, UK; Zeta Corporation, Sierra Madre, CA; Zymed Laboratories, San Diego, CA, USA. EMA: Epithelial membrane antigen; MAb: Mouse monoclonal antibody; PAb: Polyclonal antibody; SMA: Smooth muscle-type actin; MW-citrate: Microwaving for 8 min in citrate buffer (pH 6.0); AC-EDTA: Autoclaving for 100 s in EDTA buffer (pH 9.0).

Table 3 Histological features of low- and high-grade FDC sarcomas

Parameters	Low-grade phenotypes	High-grade phenotypes
Architectures	Nodular patterns in whorl, storiform and fascicular arrangement	Diffuse and sheet-like patterns
Cellular features	Spindle or blunt cells with mild nuclear atypia and a small nucleolus in > 90% of area	Epithelioid or pleomorphic cells with marked nuclear atypia and large nucleoli
Mitotic counts	< 5/10 HPF	≥ 5/10 HPF
Ki-67-LI	< 10%	≥ 10%
Necrosis	Absent	Frequently present
Lymphocyte infiltration	Sporadic and throughout the lesion	Focal or regional

Table 4 Expression of lineage-specific and kinetic-associated molecules and EBV-encoded RNA (EBER) in nine FDC sarcomas (Cases 1-9)

Cases	CK	EMA	Vimentin	CD45	CD21	CD23	CD35	Podoplanin	CD68	S-100 protein	p53 protein1	Ki-67-LI (%)	EBER
1	-	1+	3+	-	3+	NT	1+	NT	NT	NT	3+	4	NT
2	-	-	NT	-	2+	NT	2+	NT	NT	-	2+	15	NT
3	-	1+	2+	-	2+	3+	-	3+	NT	-	2+	1	-
4	-	-	3+	-	3+	2+	2+	-	-	1+	2+	8	-
5	-	-	3+	-	2+	2+	3+	2+	1+	2+	2+	15	-
6	-	-	NT	-	1+	2+	-	-	1+	1+	-	10	+
7	-	-	2+	-	1+	3+	3+	-	-	-	2+	40	-
8	-	-	1+	-	3+	2+	-	2+	2+	1+	2+	20	-
9	-	-	2+	-	1+	2+	1+	-	-	-	2+	35	-

¹Evaluated by the percentages of positive tumor cells, although majority of the positive cells showing weak nuclear immunoreactivity. Immunoreactivities expressed as strong (3+), moderate (2+), weak (1+) and negative (-); NT: Not tested.

Table 5 Clinicopathologic and therapeutic data of 97 cases of extranodal FDC sarcoma obtained from literatures (Cases 10-106)

Cases No.	Origins	Age (yr)	Gender	Size (cm)	Sites	Initial treatment (responses)	Recurrence, DFT (mo)	Status	Follow-up (mo)
10	Chan et al[24], 1994	44	M	1.5	Tonsil	Surg		NED	36
11	Chan et al[24], 1994	63	F	3	Palate	Surg + RT		NED	54
12	Hollowood et al[25], 1995	23	F	6.5	Small intestine	Surg	LR (2 times), 6	AWD	24
13	Hollowood et al[25], 1995	63	M	NA	Pancreas head	Surg	LR, 8	DOD	11
14	Nayler et al[26], 1996	18	F	2	Tonsil	Surg + ChT		NA	NA
15	Perez-Ordonez et al[16], 1996	40	F	NA	Abdomen	Surg + ChT	LR and DM (liver), 12	AWD	24
16	Perez-Ordonez et al[16], 1996	62	F	NA	Tonsil	Surg		NED	12
17	Perez-Ordonez et al[16], 1996	62	M	NA	Mediastinum	Surg + ChT	DM (lung), 24	AWD	24
18	Perez-Ordonez et al[16], 1996	46	M	NA	Mediastinum	Surg + RT		NED	12
19	Perez-Ordonez et al[16], 1996	31	M	NA	Mediastinum	Surg		NED	10
20	Perez-Ordonez et al[16], 1996	75	F	NA	Spleen	Surg	LR, 11	DOD	11
21	Selves et al[27], 1996	68	F	NA	Liver	Surg + ChT		NED	30
22	Shek et al[28], 1996	35	F	NA	Liver	Surg	LR (2 times), 30	AWD	60
23	Chan et al[3], 1997	42	M	8	Mesocolon, involving LN and peritoneum	Surg + ChT	LR, 18	DOD	18
24	Chan et al[3], 1997	32	M	NA	Tonsil	Surg + RT	LR and DM (LN), 54	AWD	54
25	Chan et al[3], 1997	40	F	7	Parapharyngeal space	Surg	LR, 12	AWD	12
26	Chan et al[3], 1997	17	M	11	Neck soft tissue	Surg + ChT		NA	NA
27	Chan et al[3], 1997	25	F	7	Neck soft tissue	Surg + RT	DM (lung), 20	AWD	20
28	Beham-Schmid et al[29], 1998	44	M	2	Nasopharynx	Surg + RT + ChT		NED	20
29	Shek et al[30], 1998	37	M	1.5	Liver	Surg		NED	24
30	Shek et al[30], 1998	61	F	4	Ampulla of Vater	Surg		NED	9
31	Araújo et al[31], 1999	14	M	1.5	Hard palate	Surg		NED	5
32	Desai et al[32], 1999	45	F	NA	Parapharyngeal space	Surg	LR, 31	NED	57
33	Fisher et al[33], 1999	41	F	2.5	Breast	Surg	LR and DM (LN), 36	NED	36
34	Galati et al[34], 1999	65	F	1.5	Thyroid	Surg + RT		NED	36
35	Schwarz et al[35], 1999	62	M	15	Abdominal wall	Surg + RT		NED	8
36	Choi et al[36], 2000	28	F	4	Neck soft tissue	Surg	DM (lung), 324	AWD	324
37	Choi et al[36], 2000	66	F	NA	Neck soft tissue	Surg + RT	DM (lung), 24	AWD	24
38	Han et al[37], 2000	45	M	5	Stomach	Surg		NED	10
39	Chan et al[38], 2001	34	M	NA	Nasopharynx	Surg		NED	36
40	Chang et al[39], 2001	37	F	5	Ascending colon	Surg		NED	7
41	Chen et al[5], 2001	57	F	9.5	Liver	Surveillance		AWD	36
42	Chen et al[5], 2001	51	F	15	Liver	Surg		NED	12
43	Chiaramonte et al[40], 2001	39	M	NA	Retroperitoneum	Surg	DM (LN and lung), 6	DOD	6
44	Shah et al[41], 2001	33	M	9.5	Lung	Surg + ChT		NA	NA
45	Biddle et al[11], 2002	33	M	NA	Pharynx	Surg + RT	DM (lung), 10	AWD	10
46	Biddle et al[11], 2002	48	F	1.5	Tonsil	Surg		NED	6
47	Biddle et al[11], 2002	48	M	3.5	Tonsil	Surg		NED	8
48	Pileri et al[2], 2002	42	M	NA	Mediastinum	Surg		NED	NA
49	Vargas et al[42], 2002	54	F	3	Tonsil	Surg		NED	8
50	Vargas et al[42], 2002	54	F	6	Left parotid	Surg + RT	LR, 6	AWD	8
51	Ceresoli et al[43], 2003	35	M	NA	Mediastinum	ChT + RT (Prog)		DOD	7
52	Satoh et al[44], 2003	16	M	3	Tonsil	Surg + RT + ChT		NED	24
53	Geerts et al[45], 2004	40	F	NA	Stomach, with DM (liver)	Surg		AWD	5
54	Grogg et al[46], 2004	62	M	NA	Left-thigh soft tissue	Surg		NED	18
55	Grogg et al[46], 2004	57	F	NA	Tonsil, involving LN	Surveillance		AWD	8
56	Grogg et al[46], 2004	64	F	14	Spleen, with DM (liver)	Surg + ChT		NED	5
57	Kröber et al[47], 2004	76	M	NA	Mediastinum	Surg + RT		NED	24
58	O’Malley[48], 2004	38	M	5	Cecum	Surg		NA	NA
59	Shi et al[49], 2004	37	M	1.5	Tonsil	Surg + ChT		NED	36
60	Bradshaw et al[50], 2005	9	M	5	Neck soft tissue	Surg	DM (lung), 60	NED	96
61	Kazakov et al[13], 2005	38	M	1.8	Skin	Surg		NA	NA
62	Khalid et al[51], 2005	19	F	16	Liver	ChT (PR)		DOD	24
63	Torres et al[52], 2005	82	M	15	Liver	Surg		NED	18
64	Aydin et al[53], 2006	76	F	3.5	Tonsil	Surg + RT		NED	48
65	Choi et al[54], 2006	68	M	NA	Dura mater	Surg + RT		NED	7
66	Clement et al[55], 2006	27	F	4	Tonsil	Surg + RT		NED	6
67	Díaz de Liaño et al[56], 2006	NA	NA	NA	Abdominal cavity	Surg	DM (liver), 18	NED	18
68	Gan et al[57], 2006	32	F	4.5	Parotid	Surg		NED	20
69	Jiang et al[58], 2006	46	F	8.4	Anterior mediastinum	ChT (stable)	DM (bone), 12	NED	19
70	Jiang et al[59], 2006	46	F	21	Pelvic/abdominal cavity, multiple	Surg		NED	6
71	Kovács et al[60], 2006	65	M	4	Lung	Surg		NED	18
72	Li et al[61], 2006	19	M	NA	Nasal cavity	Surg		NED	11
73	Lu et al[62], 2006	72	F	7	Groin	Surg		NA	NA
74	Shen et al[63], 2006	64	M	10.5	Pancreas	Surg	DM (liver), 18	NED	24
75	Shia et al[64], 2006	30	M	NA	Rectum	Surg	LR, 10	AWD	15
76	Shia et al[64], 2006	29	F	12	Lesser omentum	Surg		NED	17
77	Shia et al[64], 2006	69	F	NA	Tonsil	Surg + RT	DM (hilar LN+lung), 96	AWD	108
78	Xu et al[65], 2006	16	M	5	Adrenal	Surg		NA	NA
79	Chang et al[66], 2007	64	M	16	Chest wall	Surg		NED	15
80	Leipsic et al[67], 2007	43	M	13	Mediastinum	Surg		NA	NA
81	Padilla-Rodríguez et al[68], 2007	35	M	21	Retroperitoneal space	Surg + RT		NED	24
82	Sander et al[69], 2007	44	F	11	Spleen	Surg	DM (thorax, liver and kidney), 4	DOD	9
83	Soriano et al[70], 2007	25	F	6	Pelvis	Surg	LR, 2, 2nd Surg+RT	NED	14
84	Soriano et al[70], 2007	56	M	2	Pancreas, involving LN	Surg + RT	LR, 2	AWD	7
85	Soriano et al[70], 2007	33	M	NA	Nasopharynx	Surg + RT	LR, 10	DOD	14
86	Soriano et al[70], 2007	64	F	4	Spleen, with liver involved	Surg + ChT		AWD	29
87	Soriano et al[70], 2007	66	M	16	Pleura	ChT (Prog)		DOD	7
88	Tu et al[12], 2007	63	M	15	Jejunum mesentery	Surg		NA	NA
89	Tu et al[12], 2007	43	M	4	Appendix	Surg		NA	NA
90	Tu et al[12], 2007	28	F	15	Stomach	Surg	DM (liver), 3	AWD	3
91	Yuan et al[71], 2007	29	M	10	Liver	Surg	LR, 6	AWD	6
92	De Pas et al[72], 2008	40	F	4	Breast	Surg		NED	62
93	De Pas et al[72], 2008	53	F	NA	Liver	Surg	DM (LN), 11	DOD	22
94	De Pas et al[72], 2008	64	F	2.1	Breast	Surg		NED	20
95	Granados et al[73], 2008	57	F	13	Liver	Surg		NED	24
96	Liu et al[74], 2008	42	M	12	Gastrocolic omentum	Surg		NA	NA
97	Peng et al[75], 2008	60	M	7	Mesentery	Surg		NA	NA
98	Zhang et al[76], 2008	36	M	NA	Nasopharynx	Surg		NED	5
99	Zhang et al[76], 2008	32	F	NA	Spleen	Surg		NA	NA
100	An et al[77], 2009	40	M	5	Liver	Surg		NED	3
101	Denning et al[78], 2009	64	F	1.7	Lung	Surg		NED	24
102	Liu et al[79], 2009	75	M	4	Liver	Surg		NA	NA
103	Romero-Guadarrama et al[80], 2009	54	F	15	Thigh soft tissue	Surg	LR, 12	NED	48
104	Shen et al[81], 2009	43	M	5	Appendix	Surg	LR, 8	NED	8
105	Vaideeswar et al[82], 2009	50	M	2.5	Tonsil	Surg		NED	48
106	Xu et al[83], 2009	57	F	11	Liver	Surg		NA	NA

LN: Lymph node; NA: Not available; Prog: Disease progression.

Table 6 Associations between clinicopathological parameters and recurrence risk in patients with extranodal FDC sarcoma

Pathologic parameters	Recurrence frequencies (%)	P values
Age (yr)
< 50	26/51 (51)	0.072
≥ 50	11/35 (31)
Gender
Male	15/40 (38)	0.290
Female	22/46 (48)
Size (cm)
< 5	4/25 (16)	0.003
≥ 5	19/34 (56)
Histological grades
Low	12/37 (32)	0.046
High	15/26 (58)
Mitotic counts
< 5/10 HPF	8/30 (27)	0.013
≥ 5/10 HPF	18/31 (58)
Ki-67-LI
< 10%	2/6 (25)	0.628
≥ 10%	8/14 (57)
Necrosis
Absent	17/35 (49)	0.307
Present	13/29 (45)
Treatments
Surgery alone	22/52 (42)	0.590
Surgery + adjuvant therapy	15/31 (48)
Sites
Abdominal/pelvic	18/37 (49)	0.372
Other sites	20/53 (38)