A Prospective Cross-Sectional Study on the Comparison of Ultrasound Assessment vs. Palpation in Chronic Lymphocytic Leukemia Patients in the Era of Targeted Therapy

Abstract

Background. In IWCLL guidelines, progressive splenomegaly and lymphadenopathy are signs of active disease. In this study, we have tested the hypotheses if US could be a reliable tool for both superficial lymphnodes (SupLNs) and splenic assessment in chronic lymphocytic leukemia (CLL) patients. Methods. We enrolled N = 75 patients. SupLN and the spleen were assessed by two independent physicians (M1 and M2) by palpation and by a third physician (M3) with ultrasound sonography (US) using two different sonographers (US1 and US2). The results of M1 vs. M2 assessment, US1 vs. US2, palpation vs. US were compared. The echostructure of N = 1037 SupLN and of the spleen was also investigated. Results. The dimensions of SupLNs assessed by MD1 vs. MD2 were statistically discordant. Splenic size was concordant. There was concordance between US1 and US2 SupLN and splenic assessment. US found a higher number of pathological SupLN (Cohen’s Kappa < 0.1) than palpation, which misses remarkable-sized SupLNs. LN echostructure and splenic involvement patterns were described. Conclusions. US is a reliable, radiation-free tool useful in clinical practice to assess SupLN and splenic involvement in CLL.

Keywords: chronic lymphocytic leukemia; lymph node; spleen; ultrasound sonosgraphy.

Figure 1

Schematics of the study design.

Figure 2

Bland–Altman plots related to the comparison of the dimensions of bilateral SupLNs in the inguinal, axillary, and laterocervical regions (US1 vs. US2). US1 = Esaote ultrasonographer; US2 = GE ultrasonographer; dimensions in mm.

Figure 3

(A) N = 4 later cervical CLL SupLNs (14.9 mm, 16.4 mm, 11.7 mm, 7.9 mm). The SupLNs appear hypoechoic, without a US visible hilum, L/S < 2. The cortex appears thickened and inhomogeneous with reticulation. The SupLN present “chain”-shaped, contiguous, sharp borders. (B) Axillary CLL LN (13.6 mm). The LN appears hypoechoic, without US visible hilum, L/S ratio <2, with thickened, reticulated cortex, and sharp, regular borders. (C) Two inguinal CLL LNs (9.0 and 6.5 mm). The LNs appear hypoechoic, L/S ratio <2, with sharp borders and US-detectable hilum, although displaced and truncated (white arrowhead). The cortex is thickened, with reticulation. (D) Example of axillary CLL LN: L/S ratio >2, with visible, narrowed hilum, compressed by the thickened cortex. The cortex appears inhomogeneous (the posterior part more thickened than the anterior part). The reticulation of the cortex is prominent. (E) Axillary CLL LN, L/S ratio >2, with nonvisible hilum, sharp borders, and lobular shape. The cortex has an inhomogeneous thickening and reticulation (white arrowhead). (F) Axillary hypoechoic CLL LN, L/S ratio >2, sharp borders, without US visible hilum, with thickened, reticulated cortex (white arrow); the cortex has a polar cortical thickening (white arrowhead). (G) Axillary CLL LN (43.3 mm), L/S ratio >2, inhomogeneous, reticulated, and thickened cortex; the LN hilum is displaced and truncated (white arrowhead). (H) Example of axillary CLL LN in complete remission after treatment (liposclerotic). (I) Example of the color-doppler hilar pattern of a representative CLL axillary LN in which vessels are preserved, with regular branches reaching the peripheral part of the LN. (J) Example of chaotic, mixed color-doppler pattern of a CLL LN: sub-capsular vessels (white arrow) and intra-nodular vessels are displaced (white arrowhead). (K) Example of a hilar color-doppler pattern vascularization (white arrow) and subcapsular vascularization (white arrowheads) in the same CLL LN. (L) US-BMODE of CLL LN and vascular network using hybrid B-flow capture for enhanced microvascular details: white arrow shows the principal hilar vessel and white arrowhead shows vessels displaced irregularly, with subcapsular vessels, making the vessels network pattern overall chaotic. In panels “+” signs indicate the position of the calipers to measure the LN dimensions; “1” and, where present, “2” indicate different LNs.

Figure 4

(A) Right SC SupLNs of 13.6 mm and 14.9 mm; (B) SC left SupLNs of 21 mm and 19.6 mm. The LNs are hypoechoic, without a visible hilum, with thickened, reticulated cortex. White arrows show a focal thickening of the cortex. Arrowheads indicate the subclavian vein. The SC SupLNs were not assessable with palpation. In panels “+” signs indicate the position of the calipers to measure the LN dimensions; “1” and, where present, “2” indicate different LNs.

Figure 5

BMODE-US features contextually present in the same patient affected by CLL. (A) Left Ing LNs. (B) Right Ax LNs. The LNs of panel (A) coexist with the LNs found in the left inguinal region described in Figure 3 panels (C,D). In panels “+” signs indicate the position of the calipers to measure the LN dimensions; “1” and, where present, “2” indicate different LNs.

Figure 6

US scan of spleen in CLL patient. In (A,B) the echostructure of the spleen is finely inhomogeneous. Both longitudinal diameter (A) and cross-sectional area (B) are enlarged (15 cm and 77.7 cm², respectively). In panel (C,D), the echostructure of the spleen is finely inhomogeneous. Longitudinal diameter is within normal range (11.9 cm, panel (C)), but cross-sectional area is increased, showing that the spleen is overall enlarged (57.8 cm², panel (D)). In panels “+” signs indicate the position of the calipers to measure the spleen dimensions; “1” indicates the splenic longitudinal diameter, and “2” indicates the initial point to initiate to calculate the cross-sectional area of the spleen.

Figure 7

Patterns of splenic involvement in CLL patient. (A) Homogeneous splenomegaly. (B) Finely inhomogeneous diffuse infiltration of the spleen. (C) Micronodular diffuse B infiltration of the spleen (image obtained with a high-frequency linear probe to show the details). (D,E) Micronodular disperse hypoechoic lesions (white arrows). In panel (D) two focal, micronodular hypoechoic focal lesions are found using a convex probe, one meso-splenic and the other at the inferior pole of the spleen; in (E) one hypoechoic lesion found using a convex probe is shown. (F) The same hypoechoic lesion is shown, by scanning with a high-frequency linear probe. (G) Hypoechoic macro-nodular focal CLL lesion of the spleen found using a convex probe (white arrow). In panels “+” signs indicate the position of the calipers to measure the spleen dimensions; “1” indicates the splenic longitudinal diameter.