Hinz 2011.

Study characteristics
Patient sampling	Design: non‐comparative; prospective Country: Germany Data collection: Oct 2007 to Feb 2009 Inclusion criteria: clinically node negative, BT ≥ 1 mm or < 1 mm with risk factors such as ulceration or regression Excluded if sono‐morphological criteria for lymph node metastases
Patient characteristics and setting	Presentation: primary (pre‐SLNB but includes a secondary nodular SSM) Number patients: 81 Number primary lesions: 81 Number LNBs/metastases: NR; 170 SLNs Stage of disease: NR Mean age: 52.8 years; Median age: NR; Range: SD 15.4 years; range reported for node positive only (36 to 62 years) Male: 48 (59%) Primary lesion site: head 2, 2.5%; trunk 36, 44.4%; upper ext 14, 17.2%; lower ext 23, 28.4%; acral 6, 7.4% Breslow/Clark: median BT 1.68 mm (0.76 to 6.00 mm); 0.75 to 1.00 mm 20, 25%; 1.01 to 1.50 mm 24, 30%; 1.51 to 2.00 mm 12, 15%; 2.01 to 4.00 mm 18, 22%; > 4 mm 7, 9% Clark levels: II 1, 1%; III 26, 32%; IV 47, 58%; V 7, 9% Ulceration: 14, 17.3% Other: NR
Index tests	US: B‐mode (linear array); Doppler Machine: Nemio SSA‐550A; Toshiba Diagnostic Ultrasound System, Neuss, Germany Scan coverage: LN areas predicted by sites of melanoma Contrast: N/A FNAC: N/A Threshold: positive radiological findings according to published criteria plus PD signs of accessory peripheral vessels or displacement of intranodal vessels or asymmetrical avascular areas or aberrant course of central vessels Number observers: 1 of 4 clinicians trained in USS imaging Qualification (experience): NR; broad experience in dermato‐oncology and special ultrasound skills (NR) Diagnosis (single, consensus, etc.): unclear; appears as though single observer Info provided during test interpretation: clinical NR; likely full info available; other tests NR
Target condition and reference standard(s)	Histology (SLNB) Histological detail (n, %): H&E (serial section); IHC (S‐100, HMB 45, and Melan A); mets categorised as macro or micro mets or as cluster of cells (10 to 30 grouped cells) in the subcapsular space or interfollicular zone, or isolated melanoma cells (1 to ≤ 20 individual cells) (ref Starz 2001) (1). Histopathologist: 2 experienced dermatopathologists FNAC (n, %): NR (NR) Follow‐up (n, %): not stated (N/A) FU schedule: NR FU duration: not stated Reference blinding: NR Target condition Data: per pt Definition: nodal mets; Prevalence: 8/81 = 10%
Flow and timing	Index to histology interval: NR Index to FU interval: NR Exclusions: n = 0
Comparative
Notes	Other result: of 7 FN LNBs, 3 were classified as reactive on US and 4 were not visualised; the 2 TPs were both correctly classified pre‐LS and post‐LS. Of 8 SLN positive, all described in text as micro‐mets, but Table 2 describes 5 as > 2 mm and 3 as ≤ 2 mm; both TPs were > 2 mm
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	No
Does the study report results for participants at the same point in the clinical pathway and who would be eligible for imaging in normal practice?	Yes
Did the study report data on a per patient rather than per lesion basis?	Yes
		High	Low
DOMAIN 2: Index Test Ultrasound (pre‐SLNB)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Was the imaging test applied and interpreted in a clinically applicable manner?	Unclear
Were thresholds or criteria for diagnosis reported in sufficient detail to allow replication?	Yes
Was the test interpreted by an experienced examiner?	Unclear
		Low	Unclear
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Were the reference standard results based on patient follow‐up interpreted without knowledge of the original imaging test result?
Does the study use the same definition of disease positive as the primary review question (i.e. any mets) OR is it possible to disaggregate or regroup data such that data matching the review question can be extracted?	Yes
Was histology or cytology interpretation carried out by an experienced histopathologist or by a dermatopathologist?	Yes
		Low	Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
		Low