Villoglandular adenocarcinoma of cervix: pathologic features, clinical management, and outcome

Figures & data

Table 1 The clinical characteristics, treatment, and follow-up of patients with VGA

No	Age (years)	Chief complaint	FIGO stage	Treatment	Adjuvant treatment	Follow-up (months)	Recurrence	Outcome
1	36	Diagnosed during regular clinical examination	IA1	Conization; LRH + BS + ovarian suspension	—	11		NED
2	47	Diagnosed during regular clinical examination	IA1	Conization; LRH + BSO	—	23		NED
3	56	Cervical contactive bleeding	IB1	RAH + BSO + PLND	—	47		NED
4	52	Abnormal vaginal bleeding	IIB	RAH + BSO + high ligation of ovarian vein	NAC + RT + PC	88		NED
5	58	Postmenopausal bleeding	IA1	LRH + BSO + PLND	—	31		NED
6	33	Cervical contactive bleeding	IB1	LRH + BSO + PLND	Po-CCRT	18		NED
7	35	Diagnosed during regular clinical examination	IB1	PLND + RVT	—	19		NED
8	46	Abnormal vaginal bleeding	IB1	RAH + BSO + PLND	—	LOST		Lost
9	42	Abnormal vaginal discharge	IB2	RAH + BSO + PLND	NAC + RT + PC	32		NED
10	50	Diagnosed during regular clinical examination	IB1	RAH + BSO + PLND	—	32		NED
11	35	Cervical contactive bleeding	IB1	LRH + BS + PLND	—	25		NED
12	41	Cervical contactive bleeding	IB1	NSLRH + BSO + PLND	—	37	+	AWD
13	35	Cervical contactive bleeding	IB1	LRH + BS + PLND	—	26		NED
14	46	Cervical contactive bleeding	IB1	RAH + BSO + PLND	—	29		NED
15	66	Postmenopausal bleeding	IB1	RAH + BSO + PLND	—	104		NED
16	43	Diagnosed during regular clinical examination	IB1	Conization; RAH + BSO + PLND	—	37		NED
17	51	Cervical contactive bleeding	IB1	NSLRH + BSO + PLND	—	18		NED
18	47	Diagnosed during regular clinical examination	IB1	Conization; RAH + BSO	Pre-CCRT	37		NED
19	34	Cervical contactive bleeding	IB1	RAH + BSO + PLND	PC	35		NED
20	32	Cervical contactive bleeding	IB2	NSLRH + BSO + PLND	NAC+Po-CCRT+PC	32		NED
21	32	Abnormal vaginal discharge	IB1	LRH + BSO + PLND	—	12		NED
22	36	Abnormal vaginal discharge	IB1	Conization + UCC; CS + RAH + BS + PLND	NAC	20		NED
23	32	Cervical contactive bleeding	IB1	LRH + BS + PLND	—	12		NED
24	55	Cervical contactive bleeding	IB1	NSLRH + BSO + PLND +PALND	Po-CCRT	6		NED
25	38	Cervical contactive bleeding	IB1	NSLRH + BSO + PLND + PALND	Po-CCRT	23		NED
26	27	Abnormal vaginal discharge	IB1	PLND + RVT	PC	4		NED
27	44	Cervical contactive bleeding	IB1	LRH + BSO + PLND		12		NED
28	40	Abnormal vaginal discharge	IB1	LRH + BS + PLND		14		NED
29	49	Abnormal vaginal discharge	IIA1	RAH + BSO + high ligation of ovarian vein + PLND	Po-CCRT	20		NED
30	41	Cervical contactive bleeding	IB1	LRH + BSO + PLND		6		NED
31	40	Cervical contactive bleeding	IIB	LRH + BSO	NAC + Pre-CCRT	2		NED
32	41	Diagnosed during regular clinical examination	IB1	RAH + BSO + PLND		35		NED
33	30	Cervical contactive bleeding	IB1	Conization; NSARH + BS + PLND + PALND + ovarian suspension	Po-CCRT	49		NED
34	34	Cervical contactive bleeding	IA2	Conization; RAH + BSO + PLND	NAC+Po-CCRT	49		NED
35	45	Cervical contactive bleeding	IB1	RAH + BSO + PLND		16		NED
36	45	Cervical contactive bleeding	IB1	RAH + BSO + PLND		10		NED
37	60	Cervical contactive bleeding	IB1	LRH + BSO + PLND + PALND		11		NED
38	64	Cervical contactive bleeding	IB2	LRH + BSO	Pre-CCRT	11		NED
39	28	Cervical contactive bleeding	IB1	Conization		5		NED
40	32	Diagnosed during regular clinical examination	IB1	Conization		10		NED
41	46	Cervical contactive bleeding	IB1	RAH + BSO + PLND		59		NED

Abbreviations: VGA, villoglandular adenocarcinoma; AWD, alive with disease; BS, bilateral salpingectomy; BSO, bilateral salpingo-oophorectomy; Po-CCRT, postoperative concurrent chemoradiation therapy; Pre-CCRT, preoperative concurrent chemoradiation therapy; CS, cesarean section; LRH, laparoscopic radical hysterectomy; NAC, neoadjuvant chemotherapy; NED, no evidence of disease; NSARH, nerve-sparing abdominal radical hysterectomy; NSLRH, nerve-sparing laparoscopic radical hysterectomy; PC, postoperative chemotherapy; PALND: paraortic lymph node dissection; PLND, pelvic lymph node dissection; RAH, radical abdominal hysterectomy; RT, radiation therapy; RVT, radical vaginal trachelectomy; UCC, uterine cervical cerclage.

Table 2 Cytological test and HPV test with VGA of the cervix

Patient	Cytological test	HPV type test	HC2 HPV DNA	Clinical symptoms	Outcome
1	AGC	HPV 18+, HPV 56+		Diagnosed during regular clinical examination	NED
3	N		0.7	Cervical contactive bleeding	NED
5	ADC			Postmenopausal bleeding	NED
6	N		16.79	Cervical contactive bleeding	NED
7	HSIL		37.16	Diagnosed during regular clinical examination	NED
8	AGC			Abnormal vaginal bleeding	NED
10	N			Diagnosed during regular clinical examination	NED
11	ASCUS		1768.5	Cervical contactive bleeding	NED
12	N			Cervical contactive bleeding	AWD
13	N			Cervical contactive bleeding	NED
15	AGC			Postmenopausal bleeding	NED
16	AGC			Diagnosed during regular clinical examination	NED
18	HSIL	HPV 18+	287.1	Diagnosed during regular clinical examination	NED
19	HSIL			Cervical contactive bleeding	NED
21	ADC		84.62	Abnormal vaginal discharge	NED
22	N			Abnormal vaginal discharge	NED
23	N	HPV 16+		Cervical contactive bleeding	NED
26	AGC		114	Abnormal vaginal discharge	NED
27	HSIL			Cervical contactive bleeding	NED
28	N		5.64	Abnormal vaginal discharge	NED
29	N			Abnormal vaginal discharge	NED
30		HPV 16+		Cervical contactive bleeding	NED
32	HSIL		1402.69	Diagnosed during regular clinical examination	NED
33	N		6.87	Cervical contactive bleeding	NED
35	AGC			Cervical contactive bleeding	NED
36		HPV 16+		Cervical contactive bleeding	NED
37	ADC	HPV 16+, HPV 18+		Cervical contactive bleeding	NED
38	N			Cervical contactive bleeding	NED
39	N	HPV 16+	6.87	Cervical contactive bleeding	NED
40		HPV 16+, HPV 18+		Diagnosed during regular clinical examination	NED
41	N			Cervical contactive bleeding	NED

Abbreviations: VGA, villoglandular adenocarcinoma; ADC, adenocarcinoma; AGC, atypical glandular cell; AWD, alive with disease; ASCUS, atypical squamous cells of undetermined significance; HSIL, high-grade squamous intraepithelial lesion; N, negative; NED, no evidence of disease.

Table 3 Comparison of VGA with other ADCs of FIGO I on clinicopathological parameters

Characteristics	VGA (n=38)	ADC (n=226)	p
Age (median, range), years	41 (26–66)	42 (20–72)	0.42
FIGO stage			0.44
IA	4	31
IB1	31	151
IB2	3	44
Grade			0.000
Well	33	109
Moderate	5	70
Poor	0	45
Tumor size			0.158
≤4 cm	35	189
>4 cm	3	35
Depth of stromal invasion			0.000
≤1/2	36	145
>1/2	2	81
LVSI			0.060
Negative	37	194
Positive	1	32
Vaginal resection margin			0.433
Negative	35	215
Positive	3	11
Parametrial invasion			0.324
Negative	36	220
Positive	2	6
LN metastasis			0.001
Negative	37	194
Positive	1	32
Ovary preservation			0.239
No	29	191
Yes	9	35
Recurrence			0.038
No	37	193
Yes	1	33

Abbreviations: VGA, villoglandular adenocarcinoma; ADCs, adenocarcinomas; LN, lymph node; LVSI, lymph vascular space invasion.

Table 4 Literature review of VGA

Reference	Cases	Age	Stage	SI	LVSI	LN metastasis	Fertility preserving	Recurrence	DOD
Young and Scully^Citation6	13	33	I13 II0	≤1/2, 6 >1/2, 2	0	0	1	0	0
Kaku et al^Citation15	7	45	I10 II2	≤1/2, 4 >1/2, 3	2	2	0	1	1
Utsugi et al^Citation16	13	45	I10 II3	≤1/2, 11 >1/2, 1	4	1	ND	0	0
Khunamornpong et al^Citation17	15	39	I14 II1	≤1/2, 12 >1/2, 3	3	2	0	0	0
Jones et al^Citation7	24	37	ND	≤1/2, 23 >1/2, 1	0	0	5	0	0
Costa et al^Citation12	4	52	ND	ND	ND	ND	ND	0	0
Lataifeh et al^Citation18	28	38	I19 II7 III2	ND	ND	ND	2	3	5
Kim et al^Citation19	15	40	ND	≤1/2, 10 >1/2, 5	2	1	4	3	0
Jones et al^Citation20	12	38	ND	≤1/2, 11 >1/2, 1	ND	ND	0	2	1
Hopson et al^Citation13	3	35	I3	≤1/2, 2 >1/2, 1	0	0	0	0	0
Reed et al^Citation21	5	34.2	ND	ND	0	0	0	0	0
Korach et al^Citation22	9	38.8	I8 II1	ND	ND	ND	2	1	1
Choi et al^Citation23	3	47	ND	ND	1	1	0	0	0
Hagiwara et al^Citation24	8	36	I7 II1	≤1/2, 7 >1/2, 0	0	0	0	0	0
Stanley-Christian et al^Citation8	3	33	I3 II0	≤1/2, 3 >1/2, 1	0	0	1	1	0
Present study	41	42	I38 II3	≤1/2, 37 >1/2, 4	1	0	5	1	0

Abbreviations: VGA, villoglandular adenocarcinoma; DOD, died of disease; LN, lymph node; LVSI, lymph vascular space invasion; ND, not described; SI, stromal invasion.

YoungRHScullyREVilloglandular papillary adenocarcinoma of the uterine cervix. A clinicopathologic analysis of 13 casesCancer1989639177317792702584

 PubMed Web of Science ®Google Scholar

KakuTKamuraTShigematsuTAdenocarcinoma of the uterine cervix with predominantly villoglandular papillary growth patternGynecol Oncol19976411471528995564

 PubMed Web of Science ®Google Scholar

UtsugiKShimizuYAkiyamaFUmezawaSHasumiKClinicopathologic features of villoglandular papillary adenocarcinoma of the uterine cervixGynecol Oncol2004921647014751140

 PubMed Web of Science ®Google Scholar

KhunamornpongSMaleemonkolSSiriaunkgulSPantusartAWell-differentiated villoglandular adenocarcinoma of the uterine cervix: a report of 15 cases including two with lymph node metastasisJ Med Assoc Thai200184688288811556470

 PubMedGoogle Scholar

JonesMWSilverbergSGKurmanRJWell-differentiated villoglandular adenocarcinoma of the uterine cervix: a clinicopathological study of 24 casesInt J Gynecol Pathol1993121178418074

 PubMed Web of Science ®Google Scholar

CostaMJMcIlnayKRTrelfordJCervical carcinoma with glandular differentiation: histological evaluation predicts disease recurrence in clinical stage I or II patientsHum Pathol19952688298377635446

 PubMed Web of Science ®Google Scholar

LataifehIMAl-HussainiMUzanCJaradatIDuvillardPMoricePVilloglandular papillary adenocarcinoma of the cervix: a series of 28 cases including two with lymph node metastasisInt J Gynecol Cancer201323590090523552807

 PubMed Web of Science ®Google Scholar

KimJSungJHLeeEPrognostic factors influencing decisions about surgical treatment of villoglandular adenocarcinoma of the uterine cervixInt J Gynecol Cancer20142471299130524987921

 PubMed Web of Science ®Google Scholar

JonesMWKounelisSPapadakiHWell-differentiated villoglandular adenocarcinoma of the uterine cervix: oncogene/tumor suppressor gene alterations and human papillomavirus genotypingInt J Gynecol Pathol200019211010710782406

 PubMed Web of Science ®Google Scholar

HopsonLJonesMABoyceCRTarrazaHMJrPapillary villoglandular carcinoma of the cervixGynecol Oncol19903922212242227600

 PubMed Web of Science ®Google Scholar

ReedWAbelerVMTropéCGVillous glandular adenocarcinoma of the uterine cervix. A subtype with favourable prognosis?Tidsskr Nor Laegeforen199311320256925718236177

 PubMedGoogle Scholar

KorachJMachtingerRPerriTVilloglandular papillary adenocarcinoma of the uterine cervix: a diagnostic challengeActa Obstet Gynecol Scand200988335535819172445

 PubMed Web of Science ®Google Scholar

ChoiYKimHChoiHLiquid-based cytology of villoglandular adenocarcinoma of the cervix: a report of 3 casesKorean J Pathol201246221522023110005

 PubMedGoogle Scholar

HagiwaraTKakuTKobayashiHWakeNSaitoTWell-differentiated villoglandular adenocarcinoma of the uterine cervix: assessment of cytological features by histological subtypesActa Cytol2013571616823221334

 PubMed Web of Science ®Google Scholar

Stanley-ChristianHHeimBKHinesJFHallKLWillettGDBarnesWAVilloglandular adenocarcinoma of the cervix: a report of three cases and review of literatureGynecol Oncol19976623273309264585

 PubMed Web of Science ®Google Scholar