Sulfur Exafluoride Contrast-Enhanced Ultrasound Showing Early Wash-Out of Marked Degree Identifies Lymphoma Invasion of Spleen with Excellent Diagnostic Accuracy: A Monocentric Study of 260 Splenic Nodules

SIMPLE SUMMARY: Our retrospective collection from the database registry of the Hematology Unit of the Federico II University Medical School of Naples (Italy) of all patients referring to our center (from 1 January 2009 to 31 January 2019) for lymph node biopsy-proven lymphoma and one or more distinct splenic lesions, visible at baseline ultrasonographic scans and submitted to CEUS, could be a great asset in the diagnostic approach for splenic lymphoma. For the first time, based on a robust sample size of 260 nodules (with final diagnoses uniformly controlled by clinical laboratory imaging follow-up, in the cases not directly biopsy-proven) we showed that CEUS can achieve the diagnosis of splenic malignant lymphoma with excellent accuracy. ABSTRACT: Contrast-enhanced ultrasonography (CEUS) use for detecting lymphoma in the spleen was questioned because of the risk of its inadequate diagnostic accuracy. The aim of the present study was to validate CEUS exam for the identification of spleen involvement by lymphoma in patients at risk. A total of 260 nodules from the spleens of 77 patients with lymph node biopsy-proven non-Hodgkin lymphoma (NHL; n = 44) or Hodgkin lymphoma (HL; n = 33) at staging (n = 56) or follow-up (n = 21) were collected in a hematology Italian center and retrospectively analyzed. Nodules were classified as malignant lymphoma if ≥0.5 cm (long axis) with arterial phase isoen-hancement and early (onset <60 s after contrast agent injection) wash-out of marked (≤120 s after contrast agent injection) degree. Other perfusional combinations at CEUS scans qualified lesions as benign or inconclusive. Diagnostic reference standard was clinical laboratory imaging monitoring for 230 nodules, and/or histology for 30 nodules. The median nodule size was 1.5 cm (range 0.5–7 cm). According to the reference standard, 204 (78%) nodules were lymphomas (aggressive-NHL (a-NHL), 122; classic-HL (c-HL), 65; indolent (i)-NHL, 17) and 56 (22%) were benign (inflammation, infection, and/or mesenchymal) lesions. Sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy of CEUS for detecting lymphoma in the spleen were 95%, 100%, 100%, 85%, and 96%, respectively. Marked wash-out range of 55–90 s (median, 74 s), 92–120 s (median, 100 s), and 101–120 s (median, 114.5 s) was 100%, 96.6%, and 77% predictive of a-NHL, c-HL, and i-NHL splenic nodular infiltration, respectively. The CEUS perfusional pattern of arterial phase isoenhancement with early wash-out of marked degree was highly accurate for the detection of lymphomatous invasion of spleen in patients at risk, enabling its use for a confident non-invasive diagnosis.