Immunohistochemistry in the differential diagnosis of thyroid neoplasms

• classical papillary carcinoma

vs

papillary hyperplastic nodule

• cellular adenomatous nodules

vs

follicular variant of papillary carcinoma

Normal

Nodular goitre

Adenomatous nodule

Graves disease

Papillary hyperplastic nodule

Hashimoto's thyroiditis

Benign thyroid total

HBME-1

0/106, 0/597

1/297

0/106

0/86, 0/147

0/46

4/19(strong membrane staining occurred in small foci of non-Hurtle cells: cytoplasmic staining of Hurtle cells was considered negative.)6

4/576

CK19

10/106, 4/597

9/297

5/106

2/86, 0/147

1/4(the positive case showed staining of only 15% of cells)6

16/196

39/576

FN1

0/106, 0/597

2/297

1/106

0/86, 0/147

0/46

1/196

4/576

CITED1

10/106, 0/597

7/297

1/16

2/36, 0/147

1/16

10/106

30/316

Galectin-3

0/597

16/297

1/147

SFTPB

0/106

0/16

0/36

0/16

1/106

1/316

Ki-67

0/106

0/16

0/36

0/16

4/116

4/326

Calretinin

0/56

0/56

0/106

p16

3/56

5/56

8/106

CST6

6/86

5/76

11/156

EPS8

3/56

5/56

8/106

Cytokeratin 19

Galectin-3

negative

weak

moderate

strong

negative

weak

moderate

strong

normal thyroid

61/611

61/611

multinodular goitre

6/8(including areas of papillary hyperplasia, which were negative)1

1/81

1/81

0/81

5/8(including areas of papillary hyperplasia, which were negative)1, 5/53

0/81, 0/53

2/81, 0/53

1/81, 0/53

15/35(staining of a dominant nodule: weak staining was classified as not significant)4

20/35(staining of a dominant nodule: 12 focal and 8 diffuse staining)4

follicular adenoma

15/20(including areas of papillary hyperplasia, which were negative)1

1/201

2/20(the staining was patchy)1

2/20(although strong, the staining was extremely patchy)1

18/20(including areas of papillary hyperplasia, which were negative)1, 5/113

1/201, 5/113

0/201, 0/113

1/201, 1/113

9/32(weak staining was classified as not significant)4

23/32(10 focal and 13 diffuse staining)4

follicular carcinoma

7/121

2/121

1/121

2/121

0/121, 2/63

1/121, 1/63

6/121, 1/63

5/121, 2/63

5/19(weak staining was classified as not significant)4

14/19(5 focal and 9 diffuse staining)4

papillary carcinoma

0/221

0/221

2/221

24/221

4/221, 0/103

3/221, 1/103

1/221, 2/103

14/221, 7/103

3/38(weak staining was classified as not significant)4

35/38(7 focal and 28 diffuse staining)4

follicular variant of papillary carcinoma

0/41

0/41

0/41

4/41

1/41

0/41

0/41

3/41

anaplastic carcinoma

0/11

0/11

0/11

1/11

1/11

0/11

0/11

0/11

medullary carcinoma

0/21

0/21

1/21

1/21

1/21

0/21

0/21

1/21

classical papillary carcinoma

follicular variant of papillary carcinoma of thyroid

papillary microcarcinoma

follicular adenoma

follicular carcinoma

Hurtle cell carcinoma

Anaplastic carcinoma

papillary carcinoma vs follicular adenoma

specificity

sensitivity

HBME-1 (membrane staining5: only basolateral membranous staining is considered positive6)

43/495, 19/206, 57/677

25/295, 9/106

21/216

2/495, 0/66, 2/217

3/67

1/87

0/47

96%(vs follicular adenoma)5, 96%(vs follicular adenoma and non-neoplastic conditions)%6

87%(vs follicular adenoma)5, 93%(vs follicular adenoma and non-neoplastic conditions)%6

CK19 (cytoplasmic staining5,6)

49/495, 20/206, 48/677

26/295, 10/106

21/216

7/495, 5/66

3/67

4/87

1/47

86%(vs follicular adenoma)5, 100%(vs follicular adenoma and non-neoplastic conditions)6

96%(vs follicular adenoma)5, 32%(vs follicular adenoma and non-neoplastic conditions)6

CITED1 (membrane staining5)

44/495, 19/196, 58/677

24/295, 7/76

8/495, 6/66, 2/217

3/67

2/87

0/47

84%(vs follicular adenoma)5

87%(vs follicular adenoma)5

Galectin-3+ (cytoplasmic and some nuclear staining5)

47/495, 63/677

26/295

9/495, 2/217

4/67

7/87

4/47

82%(vs follicular adenoma)5

94%(vs follicular adenoma)5

HBME-1+ & CK19+ & Galectin-3+

42/495

23/295

0/495

100%(vs follicular adenoma)5

83%(vs follicular adenoma)5

FN1 (staining mostly weak, focal and cytoplasmic: background staining makes interpretation difficult)

20/206, 61/677

7/106

8/216

2/66, 1/217

3/67

6/87

4/47

96%(vs follicular adenoma and non-neoplastic conditions)6

93%(vs follicular adenoma and non-neoplastic conditions)6

HBME-1+ & CK19+ & FN1

35/516

SFTPB (mostly weak and focal)

5/196

0/76

0/66

Ki-67 (cytoplasmic)

18/196

0/76

0/66

Calretinin

3/106

p16

10/106

CST6

8/106

EPS8

10/106

Accuracy of Galectin-3 in differentiating thyroid malignancy from benign lesions4

sensitivity for malignancy

86%

specificity for malignancy

36%

positive predictive value

53%

negative predictive value

75%

diagnostic accuracy

59%