van Rijk 2006.

Study characteristics
Patient sampling	Design: within‐person comparison; retrospective (prospective database NR) Country: Netherlands Data collection: Nov 2000 to Dec 2004 Inclusion criteria: SLNB candidates; cutaneous MM BT > 1 mm or Clark ≥ level IV
Patient characteristics and setting	Presentation: primary (pre‐SLNB) Number patients: 107 Number primary lesions: 107 Number LNBs/metastases: NR; 37 with metastases in 42 LNBs Stage of disease: NR Mean age: 50 years; Median age: NR; Range: 15 to 52 years Male: 57 (53%) Primary lesion site: HN 6, 6%; trunk 43, 40%; arm 24, 22%; leg 34, 32% Breslow/Clark: median BT 2.0 mm (0.6 to 12.5 mm) Clark level: II 1, 1%; III 37, 35%; IV 55, 51%; V 9, 8%; undeterminable 5, 5% Ulceration: 32, 30%
Index tests	US and US plus FNAC: B‐mode linear array Machine: Siemens Elegra (Erlangen, Germany) or a Kretz Voluson 730 Expert (GE Medical Systems, Zipf, Austria) Scan coverage: NR Contrast: N/A FNAC: US positive (suspicious) underwent FNAC 21‐ or 22‐gauge needle (Figure 1), aspirated material air dried, methanol fixated and stained (May‐Grunwald‐Giemsa). FNAC+ underwent CLND Threshold: US alone suspicious ‐ length–depth ratio < 2, conversion of a fatty hilum to a hypoechoic hilum, substantial cortical asymmetry or focal area of low‐level echoes in the subcapsular sinus of the node, and diameter > 5 mm for LN of the neck. US + FNAC ‐ US positive and metastases on FNAC # Number observers: NR Qualification (experience): NR (NR) Diagnosis (single, consensus, etc.): NR Info provided during test interpretation: clinical ‐ NR; other tests ‐ NR
Target condition and reference standard(s)	Histology (SLNB; CLND) Histological detail (n, %): CLND not described; SLNB H&E (minimum 6 levels); IHC (S100, HMB45). Metastases were classified as > 2 mm in diameter or < 2 mm, as 2 mm is the current spatial resolution of ultrasonography according to Rossi et al (107, 100%). Histopathologist: NR FNAC (n, %): N/A (22 but not as part of reference standard) Follow‐up (n, %): NR (2/107; 2% (reported only for 2 positive on FNAC)) FU schedule: NR FU duration: NR Reference blinding: NR # Target condition Data: per pt Definition: nodal mets; Prevalence: 37/107 = 35%
Flow and timing	Index to histology interval: 1 to several days Index to FU interval: N/A Exclusions: n = 0
Comparative
Notes	Other result: FU of 2 FNAC positive participants is reported but no further reference to any recurrences. A breakdown of micro‐ vs macro‐metastases is also reported for those positive on histology. Of the 12 TPs on ultrasound, 7 (58%) were macro‐metastases and 5 (42%) were micro‐metastases; of the 25 FNs on US, 8 (32%) were macro‐metastases and 17 (68%) micro‐metastases The single patient who was TP on US & FNAC had macro‐metastasis; of the 36 who were FN on US & FNAC, 14 (39%) were macro‐metastases and 22 (61%) were micro‐metastases
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?	Yes
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
		Low	Low
DOMAIN 2: Index Test Ultrasound (pre‐SLNB)
Were the index test results interpreted without knowledge of the results of the reference standard?	Unclear
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
		Unclear	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?	Unclear
		Low	Unclear
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