Retrospective Analysis of Clinicopathological Features and Prognosis of Gynecological Small-Cell Carcinoma

Figures & data

Table 1 Initial Clinical Characteristics of Small-Cell Neuroendocrine Carcinoma of Gynecologic Tract for 34 Patients

Characteristics	SCNCE	SCNCO	SCNCC
	(n = 7), n (%)	(n = 7), n (%)	(n = 20), n (%)
Age
<55 years	6(85.7)	4(57.2)	2(10.0)
≥55 years	1(14.3)	3(42.8)	18(90.0)
FIGO stage
I	3(42.8)	2(28.6)	9(45.0)
II	1(14.3)	1(14.3)	8(40.0)
III	2(28.6)	3(42.8)	1(5.0)
IV	1(14.3)	1(14.3)	2(10.0)
Symptoms
Vaginal bleeding	6(85.7)	0(0.0)	4(20.0)
Abdominal distension and  abdominal pain	1(14.3)	4(57.2)	0(0.0)
Abnormal bowel  movements	0(0.0)	1(14.2)	0(0.0)
Asymptomatic	0(0.0)	2(28.6)	3(15.0)
Bleeding during intercourse	0(0.0)	0(0.0)	13(65.0)
Tumor diameter
≤4 cm	5(71.4)	0(0.0)	7(35.0)
5-9 cm	2(28.6)	2(28.6)	13(65.0)
≥10 cm	0(0.0)	5(71.4)	0(0.0)
Lymphovascular infiltration
Y	3(42.8)	2(28.6)	6(30.0)
N	4(57.2)	5(71.4)	14(70.0)
Lymph node metastasis
Y	3(42.8)	4(57.2)	8(40.0)
N	4(57.2)	3(42.8)	12(60.0)
CA125 (U/mL)
≥1000	0(0.0)	0(0.0)	–
<1000	7(100.0)	7(100.0)	–
SCC (ng/mL)
≥1.5	–	–	0(0.0)
<1.5	–	–	20(100.0)
Incisal margin
P	2(28.6)	1(14.3)	4(20.0)
N	5(71.4)	6(85.7)	16(80.0)

Abbreviations: SCNCE, small-cell neuroendocrine carcinomas of the endometrium; SCNCO, small-cell neuroendocrine carcinomas of the ovary; SCNCC, small-cell neuroendocrine carcinomas of the cervix; Y, yes; N, no; P, positive; N, negative.

Table 2 Immunohistochemical Staining Results in Small-Cell Neuroendocrine Carcinoma of Gynecologic Tract for 34 Patients

NE Markers	SCNCE (n=7)	Positive Rate %	SCNCO (n=7)	Positive Rate%	SCNCC (n=20)	Positive Rate%	Total positive Rate%
CD 56	3	42.9	6	85.7	13	65	64.7
P63	1	N	1	N	14	N	5.8
KI67	2	28.6	4	57.1	12	60	52.9
SYN	4	57.1	5	71.4	17	85	73.5
NSE	3	42.9	3	42.9	11	55	50
CK	2	28.6	3	42.9	10	50	44.1
CgA	3	42.9	3	42.9	13	65	55.9
TTF-1	3	42.9	4	57.1	1	5	23.5
P40	1	N	4	N	13	N	14.7

Abbreviations: NE, neuroendocrine; SCNCE, small-cell neuroendocrine carcinomas of the endometrium; SCNCO, small-cell neuroendocrine carcinomas of the ovary; SCNCC, small-cell neuroendocrine carcinomas of the cervix; N, negative.

Figure 1 Pathological staining images for small-cell neuroendocrine carcinoma of the gynecologic tract (SCNCGT). (A) The small-cell neuroendocrine carcinoma of the endometrium (SCNCE) was characterized by small cells with scant cytoplasm (hematoxylin and eosin stain (H&E); magnification ×200). (B) The SCNCE was positive for chromogranin A and neuron-specific enolase (H&E; original magnification, ×100). (C) The SCNCE was positive for synaptophysin (H&E; original magnification, ×100). (D) The SCNCE was positive for chromogranin A (H&E; original magnification, ×100). (E) The small-cell neuroendocrine carcinoma of the ovary (SCNCO) was characterized by small cells with scant cytoplasm (H&E; magnification ×200). (F) The SCNCO was positive for neuron-specific enolase (H&E; original magnification, ×100). (G) The SCNCO was positive for synaptophysin (H&E; original magnification, ×100). (H) The SCNCO was positive for chromogranin A (H&E; original magnification, ×100). (I) The small-cell neuroendocrine carcinoma of the cervix (SCNCC) was characterized by small cells with scant cytoplasm (H&E; magnification ×200). (J) The SCNCC was positive for neuron-specific enolase (H&E; original magnification, ×100). (K) The SCNCC was positive for synaptophysin (H&E; original magnification, ×100). (L) The SCNCC was positive for chromogranin A (H&E; original magnification, ×100).

Table 3 Treatment and Recurrence of Small-Cell Neuroendocrine Carcinoma of Gynecologic Tract for 34 Cases

Case	Stage	Pre-OP	Operation	Adjuvant Therapy	Recurrence	Interval (Months)	Location	DFS	OS
SCNCE
1	IA	N	EFH+Ad	4 EP	N			26	26
2	IA	N	EFH+Ad	4 EP	Y	6	Pelvic cavity	6	8
3	IB	N	EFH+Ad+LN+PaLN	3 EP	Y	5	Pelvic cavity	5	12
4	IIA	N	EFH+Ad+LN+PaLN	4 EP	Y	21	Pelvic cavity	21	24
5	IIIC	N	CS	6 EP	N			26	26
6	IIIC	N	CS	6 EP	Y	26	Brain and Bone	26	34
7	IVB	N	CS	1 EP	Y	1	Pelvic cavity	1	3
SCNCO
8	IA	N	UAd	6 EP	N	7		7	11
9	IA	N	SS	6 EP	Y	30	Pelvic cavity	30	36
10	IIA	N	SS	6 EP	N			16	16
11	IIIC	N	Induced+CS	4 EP	N	16	Pelvic cavity	8	24
12	IIIC	N	CS	6 BEP	N			18	18
13	IIIC	N	CS	6 BEP	Y	21	Bone	21	26
14	IVB	N	NBAC	1 TC+1 BEP	Y	3	Whole body	3	4
SCNCC
15	IB1	N	RH+LN+DOS	EP 2 cycles	Y		Lung	22	30
16	IB1	N	RH+LN+Ad	TC 6 cycles	N			31	31
17	IB1	N	RH+LN+Ad	TC 6 cycles	N			52	52
18	IB2	N	RH+LN+DOS	TC 3 cycles	N			22	22
19	IB2	N	RH+LN+Ad	TC 3 cycles + EP 2 cycles	N			7	12
20	IB3	N	RH+LV+Ad+PaLN	EP 2 cycles	Y		Brain	12	12
21	IB3	N	RH+LN+DOS+PaLN	TC 3 cycles + RT	N			6	6
22	IB3	N	RH+LN+DOS+PaLN	TC 3 cycles + RT	N			15	19
23	IB3	N	RH+LN+DOS	EP 2 cycles	N			12	16
24	IIA	N	RH+LN+Ad+PaLN	TC 3 cycles + biological treatment	N			34	34
25	IIA	N	RH+LN+Ad+PaLN	EP 2 cycles	N			48	48
26	IIA	N	RH+LN+DOS+PaLN	EP 2 cycles	N			18	18
27	IIA	TP 3 cycle	RH+LN+Ad+PaLN	TP 2 cycles	N			16	21
28	IIA	N	RH+LN+Ad+PaLN	EP 3 cycles	N			21	34
29	IIA	N	RH+LN+Ad+PaLN	TP 2 cycles + RT	Y		Brain	54	54
30	IIA	N	RH+LN+DOS+PaLN	TC 3 cycles	N			66	66
31	IIB	N	RTC		N			12	12
32	IIIb	N	RTC		N			21	21
33	IVB	N	RTC		Y		Whole body	6	7
34	IVB	N	RTC		N			5	5

Abbreviations: OP, operation; DFS, disease-free survival; OS, overall survival; SCNCE, small-cell neuroendocrine carcinoma of endometrium; RH, radical hysterectomy; EFH, extra-fascial hysterectomy; Ad, adnexectomy; EP, etoposide/cisplatin; N, no; Y, yes; LN, lymph node; Pa-LN, para-aortic lymph node resection; CS, cytoreductive surgery; NBAC, needle biopsy of the abdominal cavity; SCNCO, small-cell neuroendocrine carcinoma of ovary; UAd, unilateral adnexectomy; SS, staged surgery; TC, paclitaxel/carboplatin; BEP, bleomycin/etoposide/cisplatin; SCNCC, small-cell neuroendocrine carcinoma of cervix; RH, radical hysterectomy; DOS, double ovarian suspension; SCNCGT, small-cell neuroendocrine carcinoma of gynecologic tract; LND, lymph node dissection; RTC, radiotherapy concurrent chemotherapy; RT, radiotherapy.

Figure 2 Survival curves of all 34 patients with small-cell neuroendocrine carcinoma of the gynecologic tract (SCNCGT). (A) Kaplan–Meier curve showing the disease-free survival (DFS) rate in patients with SCNCGT. (B) Kaplan–Meier curve showing the overall survival (OS) rate in patients with SCNCGT (C) Kaplan–Meier curve showing the DFS rate in patients with small-cell neuroendocrine carcinoma of the endometrium (SCNCE), ovary (SCNCO), and cervix (SCNCC), respectively. Log rank test resulted in P = 0.131. (D) Kaplan–Meier curve showing the OS rate in patients with small-cell neuroendocrine carcinoma of the endometrium (SCNCE), ovary (SCNCO), and cervix (SCNCC), respectively. Log rank test resulted in P = 0.132. (E) Kaplan–Meier curve showing the DFS rate in patients with early-stage and advanced-stage disease, respectively. Log rank test resulted in P = 0.265. (F) Kaplan–Meier curve showing the OS rate in patients with early-stage and advanced-stage groups, respectively. Log rank test resulted in P = 0.159.