Appendix H

Melanoma: Final evidence review (July 2015) Page 154 of 876

Evidence tables for the included studies assessing immunohistochemistry FISH/molecular genetics (N=14):

FISH studies (n=7) CGH (n=1): Gerami, P et al. “Fluorescence in situ hybridization as an ancillary method for the distinction of desmoplastic melanomas from sclerosing melanocytic nevi”. J Cutan Pathol (2011) 38: 329-334.

Pub year: 2011 Patient selection Index test Reference standard Flow and timing

Country USA Retrieval of archival data of desmoplastic melanomas and sclerosing melanocytic nevi from two dermatology departments. Inclusion criteria: Diagnostically unequivocal lesions. Exclusion criteria: Diagnostically controversial or ambiguous cases.

FISH Four probes targeting Ras-responsive element-binding protein-1, myeloblastosis, cyclin D1 or chromosome 11q, and centromeric enumeration probe control for chromosome 6.

Histopathologically confirmed unequivocal lesions.

No information provided regarding the time between index test(s) and reference standard. No follow-up data.

Design, period

Retrospective case review

Was a consecutive or random sample

of patients enrolled?

No Were the index test results interpreted

without knowledge of the results of the reference

standard?

Unclear Is the reference standard likely to correctly

classify the target

condition?

Yes Was there an appropriate

interval between index test(s) and

reference standard?

Unclear

N 30 Was a case-control design avoided?

Yes If a threshold was used, was it

pre-specified?

Yes Were the reference

results interpreted

without knowledge

of the results of the index

test?

Yes Did all patients receive a reference standard?

Yes

Follow-up

Not provided

Did the study avoid inappropriate

exclusions?

Yes

Did all patients receive the same

reference standard?

Yes

Could the selection of patients have introduced bias?

Low Could the conduct or

interpretation of the index test have introduced

Low Could the reference

standard, its conduct, or

its

Low Were all patients included in the

analysis?

Yes

Appendix H

Melanoma: Final evidence review (July 2015) Page 155 of 876

bias? interpretation have

introduced bias?

Funding source

Honoraria for

consultant work at Abbott

Molecular Labs and

Neogenomics. IDP

Foundation, the

Dermatology

Foundation and the

American Cancer Society. Abbott

Molecular.

Are there concerns that the included patients do not

match the review question?

Low Are there concerns that the index test, its conduct, or interpretation differ from the

review question?

Low Are there concerns that the target

condition as defined by

the reference standard does not

match the review

question?

Low Could the patient flow have

introduced bias?

Low

Results Demographic data:

N Female/male Mean age Median age Age range

Total 30 10/20 - - -

Desmoplastic melanoma (DM) 15 2/13 67.6 71 28-92

Sclerotic melanocytic nevi (SMN) 15 8/7 41 40 24-57

FISH Disease Sensitivity specificity PPV NPV Accuracy

DM SMN

46.7 100 100 65.2 57 Positive FISH 7 0

Negative 8 15

Commen

Appendix H

Melanoma: Final evidence review (July 2015) Page 156 of 876

ts

Diaz, A et al. “Pigmented spindle cell nevus: Clues for differentiating it from spindle cell malignant melanoma. A comprehensive survey including clinicopathologic, immunohistochemical, and FISH studies”. Am J Surg Pathol (2011) 35: 1733-1742.

Pub year: 2011 Patient selection Index test Reference standard Flow and timing

Country Spain Retrieval of archival data of formalin-fixed, paraffin-embedded samples of pigmented spindle cell nevus (PSCN) and spindle cell malignant melanoma (SCMM) from one hospital clinic. Inclusion criteria: Only cases with complete uniformity of opinion of 3 blinded dermatopathologists. Exclusion criteria: Atypical forms of PSCN.

FISH 4-colour probe set targeting the ras responsive element binding protein 1 (RREB1) on 6p25, V-myb myeloblastosis viral oncogene homolog (MYB) on 6q23, cyclin D1 (CCND1) on 11q13, and the chromosome 6 centromeric region (Abbott Molecular, Des Plaines, IL)

Histopathologically examination by 3 blinded dermatopathologists.

No information provided regarding the time between index test(s) and reference standard.

Design, period

Retrospective case review

2005-2009

Was a consecutive or random sample

of patients enrolled?

No Were the index test results interpreted

without knowledge of the results of the reference

standard?

Unclear Is the reference standard likely to correctly

classify the target

condition?

Yes Was there an appropriate

interval between index test(s) and

reference standard?

Unclear

N 46 Was a case-control design avoided?

Yes If a threshold was used, was it

pre-specified?

Yes Were the reference

results interpreted

without knowledge

of the results of the index

test?

Yes Did all patients receive a reference standard?

Yes

Follow-up

Mean: 26 months

Did the study avoid inappropriate

exclusions?

Yes

Did all patients receive the same

reference standard?

Yes

Could the selection of patients have

Low Could the conduct or

Low Could the reference

Low Were all patients included in the

Yes

Appendix H

Melanoma: Final evidence review (July 2015) Page 157 of 876

introduced bias? interpretation of the index test have introduced

bias?

standard, its conduct, or

its interpretatio

n have introduced

bias?

analysis?

Funding source

Authors disclosed that they have no

significant relationship with, or financial

interest in, any

commercial

companies pertaining

to this article

Are there concerns that the included patients do not

match the review question?

Low Are there concerns that the index test, its conduct, or interpretation differ from the

review question?

Low Are there concerns that the target

condition as defined by

the reference standard does not

match the review

question?

Low Could the patient flow have

introduced bias?

Low

Results Demographic data:

N Female/male Median age Age range

Total 46 30/16 - -

Pigmented spindle cell nevus (PSCN) 22 18/4 22 3-54

Spindle cell malignant melanoma (SCMM) 24 12/12 62 26-90

FISH could be assessed in 30 of 44 cases (15 PSCN and 15 SCMM). The remaining cases were excluded because only <30 nuclei could be assessed properly or because nuclei did not show signals for all probes.

FISH Disease Sensitivity specificity PPV NPV Accuracy

SCMM PSCN

73.3 93.3 91.7 77.8 57.7 Positive FISH 11 1

Negative 4 14

Commen

Appendix H

Melanoma: Final evidence review (July 2015) Page 158 of 876

ts

Hossain, D et al. “Differential diagnosis of melanomas using fluorescence in situ hybridization (FISH) - MelanoFISH”. Conference(var.pagings): February 2011

Pub year: 2011 Patient selection Index test Reference standard Flow and timing

Country USA Skin biopsy specimens were retrospectively collected from patients with benign diagnosis, dysplastic nevi spitz nevus and melanoma. Exclusion criteria: Not provided.

FISH Probes for chromosomes 6, 7, 11 and 20.

Diagnosis independently confirmed by two dermatopathologists.

No information provided regarding the time between index test(s) and reference standard. No follow-up data.

Design, period

Retrospective case review

Was a consecutive or random sample

of patients enrolled?

Unclear Were the index test results interpreted

without knowledge of the results of the reference

standard?

Unclear Is the reference standard likely to correctly

classify the target

condition?

Yes Was there an appropriate

interval between index test(s) and

reference standard?

Unclear

N 465 Was a case-control design avoided?

Yes If a threshold was used, was it

pre-specified?

Yes Were the reference

results interpreted

without knowledge

of the results of the index

test?

Yes Did all patients receive a reference standard?

Unclear

Follow-up

Not provided

Did the study avoid inappropriate

exclusions?

Unclear

Did all patients receive the same

reference standard?

Unclear

Could the selection of patients have introduced bias?

Unclear Could the conduct or

interpretation of the index test have introduced

bias?

Low Could the reference

standard, its conduct, or

its interpretatio

n have

Low Were all patients included in the

analysis?

Unclear

Appendix H

Melanoma: Final evidence review (July 2015) Page 159 of 876

introduced bias?

Funding source

Not provided

Are there concerns that the included patients do not

match the review question?

Unclear Are there concerns that the index test, its conduct, or interpretation differ from the

review question?

Low Are there concerns that the target

condition as defined by

the reference standard does not

match the review

question?

Low Could the patient flow have

introduced bias?

Unclear

Results Sample:

N

Total 465

Benign nevi ( compound nevus, blue nevus, melanocytic nevus) (N) 205

Dysplastic nevi (clark’s, compound, junctional and residual) (DN) 55

Spitz nevi (SN) 49

Melanoma (M) 156

MelanoFISH M and DN M and SN M and N DN and SN

Disease

M

DN

SN N Sen Spe PPV NPV

Acc Sen Spe PPV NPV Acc Sen Spe PPV

NPV

Acc Sen Spe PPV NPV Acc

Positive 112 19 3 20

71.8 61.2

85.5

40.5

69.3 71.8 94.5

97.4

54.2 77.7

71.8

90.2 84.8

80.8

82.3

38.8

94.5 86.4 63.4

68.3

Negative

44 30 52 185

DN and N SN and N

38.8 90.2

48.7

86 91.8 5.5 90.2

13 78.1 74.2

The overall percent agreement between histologic diagnosis (melanoma vs. all others) and MelanoFISH results was 82%.

Appendix H

Melanoma: Final evidence review (July 2015) Page 160 of 876

Comments

Abstract of conference presentation so limited information. No demographic information provided. Unclear whether the 465 cases were all the participants included in the analysis.

Martin, V et al. “Presence of cytogenetic abnormalities in Spitz naevi: a diagnostic challenge for fluorescence in-situ hybridization analysis”. Histopathology (2012) 60: 336-346.

Pub year: 2012 Patient selection Index test Reference standard Flow and timing

Country Switzerland

Consecutive series of 82 patients with spitz naevi diagnosed between 1990-2008. Control group included 11 patients with benign nevi and 14 patients with malignant melanomas. Exclusion criteria: Spitzoid melanoma, spitz tumours of uncertain malignant potential and controversial diagnosis.

FISH Four-colour probe set LSI RREB1/LSI MYB/LSI CCND1/CEP6.

Histological review by two senior pathologists with extensive experience in neoplastic dermatopathology. Unequivocal confirmation of original diagnosis.

No information provided regarding the time between index test(s) and reference standard. Clinical follow-up available for 49 patients (of the 51 spitz naevi patients).

Design, period

Retrospective case review

Spitz naevi only:

1990-2008

Was a consecutive or random sample

of patients enrolled?

Yes Were the index test results interpreted

without knowledge of the results of the reference

standard?

Unclear Is the reference standard likely to correctly

classify the target

condition?

Yes Was there an appropriate

interval between index test(s) and

reference standard?

Unclear

N 76/107 Was a case-control design avoided?

No. Authors included controls.

Unclear if age-matched.

If a threshold was used, was it

pre-specified?

Yes Were the reference

results interpreted

without knowledge

of the results of the index

test?

Unclear

Did all patients receive a reference standard?

Yes

Follow-up

Spitz naevi only

(49/51): Median:

8.18 years Range: 2-20 years)

Did the study avoid inappropriate

exclusions?

Yes

Did all patients receive the same

reference standard?

Yes

Could the selection of patients have introduced bias?

Unclear Could the conduct or

interpretation

Low Could the reference

standard, its

Low Were all patients included in the

analysis?

No 51/82 spitz naevi gave analysable

Appendix H

Melanoma: Final evidence review (July 2015) Page 161 of 876

of the index test have introduced

bias?

conduct, or its

interpretation have

introduced bias?

results by FISH

Funding source

Abbott Molecular provided

Are there concerns that the included patients do not

match the review question?

Low Are there concerns that the index test, its conduct, or interpretation differ from the

review question?

Low Are there concerns that the target

condition as defined by

the reference standard does not

match the review

question?

Low Could the patient flow have

introduced bias?

Unclear

Results Sample:

N Female/male Mean age Age range

Total 76 - - -

Benign nevi (N) 11 - - -

Spitz naevi (SN) 51 36/15 24 1-65

Malignant melanoma (MM) 14 - - -

FISH MM and SN MM and N SN and N

Disease

MM SN N

Sensitivity

Specificity

PPV

NPV Accura

cy Sensitivit

y Specific

ity PPV NPV

Accuracy

Sensitivity

Specificity

PPV NPV Accura

cy

Positive 12 19 0 85.7 62.7

38.7

94.1 67.7 85.7 100 100 84.6

92 37.3 100 100 25.6

48.4 Negative 2 32 11

Comments

Demographic data only available for the spitz naevi group. No information on how the controls were selected. Authors state that the majority (14/19: 74%) of the FISH+ spitz naevi cases were characterised by positivity for two or three of the four diagnostic criteria, thus reducing the risk of misinterpretation.

Appendix H

Melanoma: Final evidence review (July 2015) Page 162 of 876

Kerl, K et al. “A proposal for improving multicolour FISH sensitivity in the diagnosis of malignant melanoma using new combined criteria”. Am J Dermatopathol (2012) 34: 580-585.

Pub year: 2012 Patient selection Index test Reference standard Flow and timing

Country Germany Formalin-fixed paraffin-embedded specimens were selected from the archives and consultation files of Dermatopathologie Friedrichshafen. Inclusion criteria: Not provided. Exclusion criteria: Not provided. The authors present data on all 575 lesions according to diagnosis. I selected the spitz nevus, atypical spitz tumour and Spitzoid melanoma data only 193/575.

FISH Multicolour FISH probe mix (Abbott) consisting of 4 probes used for the detection of amplifications or deletions of RREB1, MYB and CCND1 genes and of centromere 6: RREB1 (RAS responsive element-binding protein 1 encoding gene) on 6p25, MYB (myeloblastosis gene) on 6q23, CCND1 (cyclin D1 gene) on 11q13, and CEp6 (centromeric probe of chromosome 6).

Diagnosis independently confirmed by dermatopathologists using standard criteria in conjunction with hermatoxylin and eosin (H&E) – stained sections and immunohistochemical stains for MelanA, HMB45, p16, p21, phosphohistone H3 serin10, MPM2 and Ki67.

No information provided regarding the time between index test(s) and reference standard. No follow-up data provided.

Design, period

Retrospective case review

Was a consecutive or random sample

of patients enrolled?

No Were the index test

results interpreted

without knowledge of the results of the reference

standard?

Unclear Is the reference

standard likely to correctly classify the

target condition?

Yes Was there an appropriate

interval between index

test(s) and reference standard?

Unclear

N 193/575 Was a case-control design avoided?

Yes If a threshold was used, was

it pre-specified?

Yes Were the reference

results interpreted

without knowledge of the results of

the index test?

Yes Did all patients receive a reference standard?

Yes

Follow-up

Not provided

Did the study avoid inappropriate

exclusions?

Yes

Did all patients

receive the same

reference

Yes

Appendix H

Melanoma: Final evidence review (July 2015) Page 163 of 876

standard?

Could the selection of patients have introduced bias?

Low Could the conduct or

interpretation of the index

test have introduced

bias?

Low Could the reference

standard, its conduct, or its interpretation

have introduced

bias?

Low Were all patients

included in the analysis?

Yes but not all

reported in this table

Funding source

No funding information. Authors declared

no conflicts of interest.

Are there concerns that the included patients do not

match the review question?

Low Are there concerns that the index test, its conduct, or interpretation differ from the

review question?

Low Are there concerns that

the target condition as

defined by the reference

standard does not match the

review question?

Low Could the patient flow

have introduced

bias?

Low

Results Sample: N

Total 193

Spitz nevus (SN) 69

Atypical spitz tumour (AST) 90

Spitzoid melanoma (SM) 34

Disease SM and AST SM and SN AST and SN

SM AST SN

Sensitivity

Specificity

PPV NPV Accura

cy Sensitiv

ity Specific

ity PPV NPV

Accuracy

Sensitivity

Specificity

PPV NPV Accura

cy

Positive Abbott 21 47 18 61.8 47.8

30.9

76.8

51.6 61.8 73.9 53.8

79.7

69.9 52.2 73.9 72.3

54.3

61.6 Negative 13 43 51

Positive Gerami 22 54 16 64.7 40

28.9

75 46.8 64.7 76.8 57.9

81.5

72.8 60 76.8 77.1

59.6

67.3 Negative 12 36 53

Positive 24 56 22 70.6 37.8 30 77. 46.8 70.6 68.1 52. 82. 68.9 62.2 68.1 71. 58 64.8

Appendix H

Melanoma: Final evidence review (July 2015) Page 164 of 876

Combined 3 2 5 8

Negative 10 34 47

Comments

No demographic data provided on sample.

Massi, D et al. “Atypical Spitzoid melanocytic tumors: a morphological, mutational, and FISH analysis”. Dermatopathology (2011) 64: 919-935.

Pub year: 2011 Patient selection Index test Reference standard Flow and timing

Country Italy Atypical spizoid lesions: Archival data from pathology files of three hospitals (n=38). Comparator: independent cohort of unambiguously classified as Spitz nevi and unequivocal melanomas (n=20). Inclusion criteria: Patients whose tumors measured at least 1mm in thickness. Exclusion criteria: Not provided.

FISH Multicolor FISH DNA kit composed from LSI RRED1 (6p25) SpectrumRed/LSI MYB (6q23) SpectrumGold/LSI CCND1 (11q13) SpectrumGreen/CEp6 (6p11.1-q11 Alpha Satellite DNA) SpectrumAgua.

For the atypical Spitzoid lesions: Histopathological slides independently reviewed and then re-evaluated on the multiheaded microscope by 4 pathologists with specific background in dermatopathology. For the unambiguously classified spitz nevi and unequivocal melanomas: reviewed by at least two dermatopathologists who agreed the diagnosis.

No information provided regarding the time between index test(s) and reference standard. Clinical follow-up available for 49 patients (of the 51 spitz naevi patients).

Design, period

Retrospective case review

Was a consecutive or random sample

of patients enrolled?

No Were the index test results interpreted

without knowledge of the results of the

reference standard?

Unclear Is the reference standard likely to

correctly classify the target condition?

Yes Was there an appropriate

interval between index

test(s) and reference

Unclear

Appendix H

Melanoma: Final evidence review (July 2015) Page 165 of 876

standard?

N 45/58 Was a case-control design

avoided?

No If a threshold was used, was it pre-

specified?

Yes Were the reference results interpreted

without knowledge of the results of the

index test?

Yes Did all patients receive a reference standard?

Yes

Follow-up

8 months – 13 years Mean: 4 years 10 months

Did the study avoid

inappropriate exclusions?

Unclear

Did all patients

receive the same

reference standard?

No. The control

group only assessed by

2 dermatopath

ologists

Could the selection of

patients have introduced bias?

Unclear Could the conduct or interpretation of the

index test have introduced bias?

Low Could the reference standard, its conduct, or its interpretation

have introduced bias?

Low Were all patients

included in the analysis?

No. 13 of the AST did not perform in

the FISH analysis

Funding source

Supported in part by

Abbott Molecular

Inc. ACC/R8.5 research project,

and Fondazion

e Ente Cassa di

Risparmio di Firenze.

Are there concerns that the included patients do not match the review question?

Low Are there concerns that the index test, its

conduct, or interpretation differ

from the review question?

Low Are there concerns that the target

condition as defined by the reference

standard does not match the review

question?

Low Could the patient flow

have introduced

bias?

Low

Results Sample:

N Female/male Mean age Age range

Total 45/58 - - -

Appendix H

Melanoma: Final evidence review (July 2015) Page 166 of 876

Spitz naevi (SN) 10 - - -

Atypical Spitzoid tumours (AST)

25/38 21/17 24 1-65

Melanoma (M) 10 - - -

Only 25/38 atypical Spitzoid tumours performed in the FISH analysis. FISH

M and AST M and SN AST and SN Disease

M AST

SN

Sensitivity Specificity PPV NPV

Accurac

y

Sensitivity

Specificity

PPV NPV

Accuracy Sensitivit

y Specifi

city PPV NPV

Accurac

y

Positive 9 6 2 90 76 60 95 80 90 80 81.8

88.

9 85 24 80 75 29.6

4

0 Negative 1 19 8

Comments

Demographic data only available for the atypical Spitzoid tumour group. No information on how the controls were selected.

Requena, C et al. “Fluorescence in situ hybridization for the differential diagnosis between spitz naevus and Spitzoid melanoma”. Histopathology (2012) 61: 899-909.

Pub year: 2012 Patient selection Index test Reference standard Flow and timing

Country Spain All cases of Spitzoid melanomas treated at one hospital assessed. N= 17. Comparator: Cases of spitz naevi from hospital files included. N = 6. Inclusion criteria: Not provided. Exclusion criteria: Two cases of Spitzoid melanoma excluded as the original biopsies could not be obtained, two because of doubts in the differential diagnosis and one because the Spitzoid area accounted for <25% of the biopsy specimen. N=5.

FISH Vysis Melanoma FISH Probe Kit (Abbott Molecular Inc., Des Plaines, IL). Designed to detect the copy number of RREB1, MYB and CCND1 genes and of centromere 6 labelled with SpectrumRed, SpectrumGold, SpectrumGreen and SpectrumAqua.

Histopathological diagnosis based on histopathological features (Requena et al., 2012)

No information provided regarding the time between index test(s) and reference standard.

Design, period

Retrospective case review

2008-2011

Was a consecutive or random sample

of patients enrolled?

No Were the index test

results interpreted

without

Unclear Is the reference standard likely to correctly

Yes Was there an appropriate

interval between index

test(s) and

Unclear

Appendix H

Melanoma: Final evidence review (July 2015) Page 167 of 876

knowledge of the results of the reference

standard?

classify the target

condition?

reference standard?

N 18 Was a case-control design

avoided?

No If a threshold was used, was it pre-specified?

Yes Were the reference

results interpreted

without knowledge

of the results of the index

test?

Yes Did all patients receive a reference standard?

Yes

Follow-up

Range: 2-82 months

Did the study avoid

inappropriate exclusions?

Yes

Did all patients receive the

same reference standard?

Yes

Could the selection of

patients have introduced bias?

Unclear Could the conduct or

interpretation of the index

test have introduced

bias?

Low Could the reference standard,

its conduct, or its

interpretation have

introduced bias?

Low Were all patients

included in the analysis?

No

Funding source

Conselleria de

sanitat of the

generalitat

valenciana.

Are there concerns that the included patients do not match the review question?

Low Are there concerns that

the index test, its

conduct, or interpretation differ from the review question?

Low Are there concerns that the target

condition as defined by

the reference standard does not

match the review

question?

Low Could the patient flow

have introduced

bias?

Low

Appendix H

Melanoma: Final evidence review (July 2015) Page 168 of 876

Results Sample:

N Female/male Mean age Age range

Total 18 12/6 - -

Spitz naevi (SN) 6 4/2 - 7-38

Spitzoid Melanoma (SM)

12 8/4 - 19-56

Only 8/12 Spitzoid melanomas performed in the FISH analysis. 5/6 spitz naevi performed in the FISH analysis.

FISH Disease Sensitivity specificity PPV NPV Accuracy

SM SN

87.5 100 100 83.33333 92.3 Positive FISH (Abbott criteria) 7 0

Negative 1 5

Positive FISH (Gerami et al. criteria)

8 0 100 100 100 100 100

Negative 0 5

Comments

Demographic data only available for the atypical Spitzoid tumour group. No information on how the controls were selected.

Appendix H

Melanoma: Final evidence review (July 2015) Page 169 of 876

Bastian, BC et al. “Classifying melanocytic tumors based on DNA copy number changes”. American Journal of Pathology (2003) 163: 1765-1770.

Pub year: 2003 Patient selection Index test Reference standard Flow and timing

Country USA and Germany

Paraffin-embedded primary invasive melanomas retrieved from archives at two hospitals. Inclusion criteria: Cases were required to have at least one area from which a rather pure population of tumor cells could be isolated to yield sufficient amounts of DNA for CGH analysis. Exclusion criteria: Not provided. Of the 54 benign nevi (27 spitz nevi; 19 blue nevi; 7 congenital nevi) only the 27 spitz nevi will be reported.

DNA extraction and Comparative Genomic Hybridization (CGH). Results interpreted blinded to the histopathological information.

Histopathological diagnosis No information provided regarding the time between index test(s) and reference standard.

Design, period

Retrospective case review

Was a consecutive or random sample

of patients enrolled?

No Were the index test

results interpreted

without knowledge of the results of the reference

standard?

Yes Is the reference standard likely to correctly

classify the target

condition?

Yes Was there an appropriate

interval between index

test(s) and reference standard?

Unclear

N 159/186 Was a case-control design avoided?

Yes If a threshold was used, was

it pre-specified?

Yes Were the reference

results interpreted

without knowledge

of the results of the index

test?

Yes Did all patients receive a reference standard?

Yes

Follow-up

Not provided

Did the study avoid inappropriate

exclusions?

Yes

Did all patients receive the

same reference standard?

Yes

Could the selection of patients have introduced bias?

Low Could the conduct or

interpretation

Low Could the reference

standard, its

Low Were all patients

included in the

Yes. But not presented

in this table

Appendix H

Melanoma: Final evidence review (July 2015) Page 170 of 876

of the index test have

introduced bias?

conduct, or its

interpretation have

introduced bias?

analysis?

Funding source

Roma and Marvin

Auerback Melanoma

Fund

Are there concerns that the included patients do not

match the review question?

Low Are there concerns that the index test, its conduct, or interpretation differ from the

review question?

Low Are there concerns that the target

condition as defined by

the reference standard does not

match the review

question?

Low Could the patient flow

have introduced bias?

Low

Results Sample:

N Female/male Mean age

Total 186 89/97 53.7

Benign nevi (blue nevi, congenital nevi) 27 - -

Spitz nevi (SN) 27 - -

Malignant Melanoma (MM) 132 65/67 68

Of the 54 benign nevi (27 spitz nevi; 19 blue nevi; 7 congenital nevi) only the 27 spitz nevi will be reported.

CGH Disease Sensitivity specificity PPV NPV Accuracy

MM SN

96.2 74.1 94.8 80 92.5 At least one chromosomal aberration

127 7

No aberrations 5 20

Comments

CGH findings of 79 cases has been published previously.