Diagnostic Accuracy of Brush Cytology with Direct Smear and Cell-block Techniques according to Preparation Order and Tumor Characteristics in Biliary Strictures

Yeong Geol Jo; Tae Hoon Lee; Hyun-Deuk Cho; Sang-Heum Park; Jae Man Park; Young Sin Cho; Yunho Jung; Il-Kwun Chung; Hyun Jong Choi; Jong Ho Moon; Sang Woo Cha; Young Deok Cho; Sun-Joo Kim

doi:10.4166/kjg.2014.63.4.223

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Jo, Lee, Cho, Park, Park, Cho, Jung, Chung, Choi, Moon, Cha, Cho, and Kim: Diagnostic Accuracy of Brush Cytology with Direct Smear and Cell-block Techniques according to Preparation Order and Tumor Characteristics in Biliary Strictures

Original Article

Korean J Gastroenterol 2014;63(4):223-230.

Published online: 4 October 2014

DOI: https://doi.org/10.4166/kjg.2014.63.4.223

Diagnostic Accuracy of Brush Cytology with Direct Smear and Cell-block Techniques according to Preparation Order and Tumor Characteristics in Biliary Strictures

Yeong Geol Jo, Tae Hoon Lee, Hyun-Deuk Cho¹, Sang-Heum Park, Jae Man Park, Young Sin Cho, Yunho Jung, Il-Kwun Chung, Hyun Jong Choi², Jong Ho Moon², Sang Woo Cha³, Young Deok Cho³, Sun-Joo Kim

Department of Internal Medicine, Soonchunhyang University Hospital Cheonan, Korea

¹Department of Pathology, Soonchunhyang University Hospital Cheonan, Korea

²Department of Internal Medicine, Soonchunhyang University Hospital Bucheon, Soonchunhyang University College of Medicine, Korea

³Department of Hospital Seoul, Soonchunhyang University College of Medicine, Korea

Correspondence to: Tae Hoon Lee, Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University Hospital Cheonan, 31 Suncheonhyang 6-gil, Dongnam-gu, Cheonan 330-903, Korea. Tel: +82-41-570-3662, Fax: +82-41-574-5762, E-mail: thlee9@schmc.ac.kr

Received 4 January 2014 Revised 26 February 2014 Accepted 28 February 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims

There are few data supporting the diagnostic yield of brush cytology depending on the order of cytologic preparation method or the location or shape of tumors in biliary strictures. We investigated diagnostic yields and variations in brush cytology with direct smear and cell-block preparations according to sampling preparation sequence and tumor location and shape in biliary strictures.

Methods

Patients who had undergone ERCP with tissue sampling between August 2009 and April 2013 were analyzed retrospectively. Group A was examined using brush cytology with direct smear followed by cell-block with or without biopsy, while the reverse order was performed for group B.

Results

Among 138 enrolled patients, 92 patients (A: 36, B: 56) underwent both brush cytology with direct smear and cell-block preparations. No differences in sensitivity, specificity, or accuracy were observed according to the sampling preparation method and the location or shape of tumors in biliary strictures. The cellularity observed from brush cytology with direct smear was better than that from cell-block according to the location of the tumor (p＜0.01). The diagnostic yield was increased in both groups with addition of an endobiliary biopsy.

Conclusions

No difference in diagnostic accuracy was observed between the sequences of preparation for brush cytology with direct smear and cell-block techniques. Brush cytology showed better cellularity for diagnosis.

Keywords: Biliary stricture, Brush cytology, Cell-block

References

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Table 1.

Baseline Characteristics

Clinical characteristics	Value
Patient	138 (100)
Male/female	83 (60.1)/55 (39.9)
Age (yr)	67.9±11.7
Clinical diagnosis
Malignant	113 (81.8)
Cholangiocarcinoma	81 (58.6)
Pancreatic cancer	24 (17.3)
Gallbladder cancer	3 (2.1)
Hepatocellular carcinoma	2 (1.4)
Others^a	3 (2.1)
Benign	25 (18.1)
Location of lesion (malignant/benign)
Intrahepatic	9 (7.9)/4 (16.0)
Perihilar	40 (35.3)/1 (4.0)
Extrahepatic	62 (54.8)/17 (68.0)
Pancreatic duct	2 (1.7)/3 (12.0)
Cholangiographic appearance
Protuberant (nodular)	16 (20.2)/4 (5.0)
Papillary protuberant	6 (7.5)/0 (0)
Sclerosed	29 (36.7)/11 (13.9)
Constricted	11 (13.9)/2 (2.5)
Laboratory finding
ALP (IU/L)	407.0±317.7
Total bilirubin (mg/dL)	9.2±9.46
CA 19–9 (U/mL)	1,499.3±4,895
CEA (ng/mL)	13.6±77.9

Values are presented as number (%) or mean±SD.

^a Thymic carcinoma, periampullary carcinoma.

Table 2.

Baseline Characteristics in Brush Cytology Depending on the Order of Cytologic Preparation Methods

Subgroup characteristics	Group A	Group B	p-value
Patient	36 (100)	56 (100)
Male/female	21 (58.3)/15 (41.6)	30 (53.5)/26 (46.4)	0.654
Age (yr)	66.5±12.6	71.6±10.2	0.048
Clinical diagnosis
Malignant/benign	31 (86.1)/5 (13.8)	46 (82.1)/10 (17.8)	0.615
Malignant	31 (100)	46 (100)
Cholangiocarcinoma	23 (74.1)	30 (65.2)
Pancreatic cancer	4 (12.9)	14 (30.4)
GB cancer	1 (3.2)	2 (4.3)
Others^a	3 (9.6)	−
Location of lesion			−
Intrahepatic	4 (11.1)	5 (8.9)
Perihilar	11 (30.5)	20 (35.7)
Extrahepatic	19 (52.7)	28 (50.0)
Pancreatic duct	2 (5.5)	3 (5.3)
Cholangiographic appearance			−
Protuberant (nodular)	5 (13.8)	10 (27.7)
Papillary protuberant	−	3 (5.3)
Sclerosed	25 (69.4)	39 (69.6)
Constricted	6 (16.6)	4 (7.1)
Laboratory finding
ALP (IU/L)	359.0±329.4	455.0±319.0	0.169
Total bilirubin (mg/dL)	7.6±8.9	9.7±9.2	0.265
CA 19–9 (U/mL)	1,763±5,313	2,306±6,329	0.675
CEA (ng/mL)	30.6±153.1	10.8±18.98	0.459

Values are presented as n (%) or mean±SD.

GB, gall bladder.

Group A, brush cytology with direct smear followed by cell-block; group B, brush cytology with cell-block followed by direct smear.

^a Thymic carcinoma, periampullary carcinoma.

Table 3.

Diagnostic Yield of Endobiliary Forceps Biopsy, Brush Cytology with Direct Smear and Cell-block

Variable	Endobiliary forceps biopsy^a	Brush cytology
Variable	Endobiliary forceps biopsy^a	Direct smear^b	Cell-block^c
Sensitivity	32/66 (48.4)	59/97 (60.8)	35/62 (56.4)
Specificity	11/12 (91.6)	20/20 (100)	8/9 (88.8)
PPV	32/33 (96.9)	59/59 (100)	35/36 (97.2)
NPV	11/45 (24.4)	20/58 (34.4)	8/35 (22.8)
Accuracy	43/78 (55.1)	79/117 (67.5)	43/71 (60.5)

Values are presented as n/total (%).

PPV, positive predictive value; NPV, negative predictive value.

^a Non-diagnostic cases (5 of 83)

^b non-diagnostic cases (6 of 123)

^c non-diagnostic cases (21 of 92).

Table 4.

Diagnostic Yields of Brush Cytology with or without Endobiliary Forceps Biopsy

Variable	Both techniques^a			Triple techniques^b
Variable	Group A^c	Group B^d	p-value	Group A	Group B	p-value
Sensitivity	18/31 (58.0)	30/46 (65.2)	0.525	10/13 (76.9)	18/29 (62.0)	0.485
Specificity	5/5 (100)	9/10 (90.0)	＞0.999	1/1 (100)	3/3 (100)	−
PPV	18/18 (100)	30/31 (96.7)	＞0.999	10/10 (100)	18/18 (100)	−
NPV	5/18 (27.7)	9/25 (36.0)	0.570	1/4 (25.0)	3/14 (21.4)	＞0.999
Accuracy	23/36 (63.8)	39/56 (69.6)	0.566	11/14 (78.5)	21/32 (68.7)	＞0.999

Values are presented as n/total (%).

PPV, positive predictive value; NPV, negative predictive value.

^a Brush cytology with direct smear and cell-block preparation.

^b Endobiliary forceps biopsy, brush cytology with direct smear and cell-block preparation.

^c Non-diagnostic cases (14 of 36)

^d non-diagnostic cases (9 of 56).

Table 5.

Cellularity of Brush Cytology and Preparation Methods (Group A and B) according to Location of Malignant Lesion

Location of lesion	Cellularity	Brush cytology		p-value	Group A	Group B	p-value
Location of lesion	Cellularity	Direct smear	Cell-block	p-value	Group A	Group B	p-value
Total	Good	51 (50.0)	17 (22.1)	＜0.01	19 (61.3)	27 (58.7)	＞0.999
	Fair	34 (33.3)	29 (37.7)		10 (32.3)	15 (32.6)
	Poor	17 (16.7)	31 (40.3)		2 (6.5)	4 (8.7)
Intrahepatic	Good	2 (25.0)	1 (16.7)	0.391	2 (66.7)	1 (33.3)	0.400
	Fair	4 (50.0)	2 (33.3)		0 (0)	2 (66.7)
	Poor	2 (25.0)	3 (50.0)		1 (33.3)	0 (0)
Perihilar	Good	24 (60.0)	9 (30.0)	＜0.01	6 (54.6)	15 (79.0)	0.081
	Fair	11 (27.5)	10 (33.3)		5 (45.5)	2 (10.5)
	Poor	5 (12.5)	11 (36.7)		0 (0)	2 (10.5)
Extrahepatic	Good	24 (46.2)	7 (18.0)	＜0.01	10 (62.5)	11 (47.8)	0.778
	Fair	18 (34.6)	16 (41.0)		5 (31.3)	10 (43.5)
	Poor	10 (19.2)	16 (41.0)		1 (6.3)	2 (8.7)
Pancreatic duct	Good	1 (50.0)	0 (0)	−	1 (100)	0 (0)	−
	Fair	1 (50.0)	1 (50.0)		0 (0)	1 (100)
	Poor	0 (0)	1 (50.0)		0 (0)	0 (0)

Values are presented as n (%).

Group A, brush cytology with direct smear followed by cell-block; group B, brush cytology with cell-block followed by direct smear.

Table 6.

Diagnostic Yield of Preparation Methods (Group A and B) according to Location of Lesion

Location of lesion	Yield	Group A	Group B	p-value
Intrahepatic	Sensitivity	2/3 (66.6)	3/3 (100)	＞0.999
	Specificity	1/1 (100)	1/2 (50.0)	＞0.999
	PPV	2/2 (100)	3/4 (75.0)	＞0.999
	NPV	1/2 (50.0)	1/1 (100)	＞0.999
	Accuracy	3/4 (75.0)	4/5 (80.0)	＞0.999
Perihilar	Sensitivity	8/11 (72.7)	13/19 (68.4)	＞0.999
	Specificity	−	1/1 (100)	−
	PPV	8/8 (100)	13/13 (100)	−
	NPV	−	1/7 (14.2)	＞0.999
	Accuracy	8/11 (72.7)	14/20 (70.0)	＞0.999
Extrahepatic	Sensitivity	8/16 (50.0)	13/23 (56.5)	0.752
	Specificity	3/3 (100)	5/5 (100)	−
	PPV	8/8 (100)	13/13 (100)	−
	NPV	3/11 (27.2)	5/15 (33.3)	＞0.999
	Accuracy	11/19 (57.8)	18/28 (64.2)	0.763
Pancreatic duct	Sensitivity	−	1/1 (100)	＞0.999
	Specificity	1/1 (100)	2/2 (100)	−
	PPV	−	1/1 (100)	−
	NPV	1/1 (100)	2/2 (100)	−
	Accuracy	1/2 (50.0)	3/3 (100)	0.400

Values are presented as n/total (%).

Group A, brush cytology with direct smear followed by cell-block; group B, brush cytology with cell-block followed by direct smear.

PPV, positive predictive value; NPV, negative predictive value.

Table 7.

Cellularity of Preparation Methods (Group A and B) according to the Cholangiographic Appearance of Extrahepatic Malignancy

Cholangiographic appearance	Celularity	Group A	Group B	p-value
Total	Good	10 (62.5)	11 (47.8)	0.778
	Fair	5 (31.3)	10 (43.5)
	Poor	1 (6.3)	2 (8.7)
Protuberant	Good	2 (66.7)	3 (42.9)	＞0.999
	Fair	1 (33.3)	3 (42.9)
	Poor	0 (0)	1 (14.3)
Papillary	Good	−	0 (0)	−
	Fair	−	2 (66.7)
	Poor	−	1 (33.3)
Sclerosed	Good	5 (62.5)	8 (66.7)	＞0.999
	Fair	3 (37.5)	4 (33.3)
	Poor	0 (0)	0 (0)
Constricted	Good	3 (60.0)	0 (0)	0.500
	Fair	1 (20.0)	1 (100)
	Poor	1 (20.0)	0 (0)

Values are presented as n (%).

Group A, brush cytology with direct smear followed by cell-block; group B, brush cytology with cell-block followed by direct smear.

Table 8.

Diagnostic Yield of Preparation Methods (Group A and B) according to the Cholangiographic Appearance

Cholangiographic appearance	Yield	Group A	Group B	p-value
Protuberant	Sensitivity	3/5 (60.0)	3/7 (42.8)	＞0.999
	Specificity	−	2/3 (66.6)	−
	PPV	3/3 (100)	3/4 (75.0)	＞0.999
	NPV	−	2/6 (33.3)	＞0.999
	Accuracy	3/5 (60.0)	5/10 (50.0)	＞0.999
Papillary	Sensitivity	−	1/3 (33.3)	−
	Specificity	−	−	−
	PPV	−	1/1 (100)	−
	NPV	−	−	−
	Accuracy	−	1/3 (33.3)	−
Sclerosed	Sensitivity	13/21 (61.9)	25/33 (75.7)	0.362
	Specificity	4/4 (100)	6/6 (100)	−
	PPV	13/13 (100)	25/25 (100)	−
	NPV	4/12 (33.3)	6/14 (42.8)	0.701
	Accuracy	17/25 (68.0)	31/39 (79.4)	0.378
Constricted	Sensitivity	2/5 (40.0)	1/3 (33.3)	＞0.999
	Specificity	1/1 (100)	1/1 (100)	−
	PPV	2/2 (100)	1/1 (100)	−
	NPV	1/4 (25.0)	1/3 (33.3)	＞0.999
	Accuracy	3/6 (50.0)	2/4 (50.0)	＞0.999

Values are presented as n/total (%).

Group A, brush cytology with direct smear followed by cell-block; group B, brush cytology with cell-block followed by direct smear.

PPV, positive predictive value; NPV, negative predictive value.

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