Neoplasm

Mean NS5

Median NS

Pleomorphism6

Cellularity

ISK1

117

110

57

398

VV2

216

201

92

127

HAK3

223

210

111

83

SCC4

231

218

126

66

1: Irritated seborrheic keratosis 2: Verruca vulgaris 3: Hypertrophic actinic keratosis 4: Squamous cell carcinoma 5: Nuclear Size 6: Pleomorphism measured via the standard deviation of the nuclear size

Table 1: Image Analysis Characteristics of the Known Neoplasms

Neoplasm

NS5 Range6

Pleomorphism Range7

Cellularity Range8

ISK1

61-173

49-65

200-596

VV2

124-307

74-110

52-202

HAK3

112-334

89-133

50-116

SCC4

105-357

95-157

32-100

1: Irritated seborrheic keratosis 2: Verruca vulgaris 3: Hypertrophic actinic keratosis 4: Squamous cell carcinoma 5: Nuclear Size 6: Created by taking the NS +/- 1 standard deviation 7: Created by taking the NS standard deviation +/- 1 standard deviation 8: Created by taking the Cellularity +/- 1 standard deviation

Table 2: Diagnostic Ranges

Case

Mean NS1

Possibilities

IA Diagnosis

Clinical Correlation

Case 1

115

ISK2

Benign

Benign

Case 2

297

VV3, HAK4, SCC5

Indeterminate *

Benign

Case 3

536

SCC

Malignant

Malignant

Case 4

209

VV, HAK, SCC

Indeterminate

Benign

Case5

300

VV, HAK, SCC

Indeterminate

Benign

Case 6

267

VV, HAK, SCC

Indeterminate

Malignant

Case 7

342

SCC

Malignant

Malignant

Case 8

355

SCC

Malignant

Benign

Case 9

197

VV, HAK, SCC

Indeterminate

Benign

Case 10

412

SCC^

Malignant

Malignant

1: Nuclear Size 2: Irritated seborrheic keratosis 3: Verruca vulgaris 4: Hypertrophic actinic keratosis 5: Squamous cell carcinoma *: When cases could not be reliably classified as Benign or Pre-malignant/Malignant, they were classified as Indeterminate. ^: In instances where the NS exceeded the highest value of the NS diagnostic ranges, the IA diagnosis rendered was that of SCC. Blue: Designates an IA diagnosis that correctly correlates with the clinical course. Red: Designates an IA diagnosis that incorrectly correlates with the clinical course.

Table 3a: Diagnosing Transected Neoplasms using the Nuclear Size Diagnostic Range

Case

Pleomorpism

Possibilities

Plemorphism Diagnosis

Clinical Correlation

Case 1

42

ISK1*

Benign

Benign

Case 2

83

VV2

Benign

Benign

Case 3

191

SCC3

Malignant

Malignant

Case 4

50

ISK4

Benign

Benign

Case5

94

VV, HAK

Indeterminate

Benign

Case 6

108

VV, HAK, SCC

Indeterminate

Malignant

Case 7

125

HAK, SCC

Malignant

Malignant

Case 8

65

ISK

Benign

Benign

Case 9

82

VV

Benign

Benign

Case 10

144

SCC

Malignant

Malignant

1: Irritated seborrheic keratosis 2: Verruca vulgaris 3: Hypertrophic actinic keratosis 4: Squamous cell carcinoma *: In instances where the pleomorphism fell below the lowest value of the Pleomorphism diagnostic ranges, the IA diagnosis rendered was that of ISK.

Table 3b: Diagnostic Ranges

Case

Cellularity

Possibilities

Cellularity Diagnosis

Clinical

Case 1

215

ISK1

Benign

Benign

Case 2

42

SCC

Malignant

Benign

Case 3

36

SCC

Malignant

Malignant

Case 4

93

VV2, HAK3, SCC4

Indeterminate

Benign

Case5

86

VV, HAK, SCC

Indeterminate

Benign

Case 6

108

VV

Benign

Malignant

Case 7

71

VV, HAK, SCC

Indeterminate

Malignant

Case 8

69

VV, HAK, SCC

Indeterminate

Benign

Case 9

216

ISK

Benign

Benign

Case 10

63

VV, HAK, SCC

Indeterminate

Malignant

1: Irritated seborrheic keratosis 2: Verruca vulgaris 3: Hypertrophic actinic keratosis 4: Squamous cell carcinoma

Table 3c: Diagnosing Transected Neoplasms using the Cellularity Diagnostic Range

Figure 1: Example of Image Anaysis performed on a Known Neoplasm 1a: H&E image of a known hypertrophic actinic keratosis neoplasm (original magnification x 20). 1b: A representative area of stratum spinosum is selected comprising 210,000 pixels. 1c: Nuclei are selected out. 1d: Image analysis carried out using Image J software.