Preoperative CT Predicting Recurrence of Surgically Resected Adenocarcinoma of the Lung

Abstract

Pathologic lymphovascular invasion (LVI) has been shown to be related to tumor recurrence in lung adenocarcinoma (ADC). We investigated preoperative computed tomography (CT) findings that may be related to pathologic LVI and recurrence of surgically managed stage I-II ADC of the lung.Consecutive patients (n = 275) with ADC from January 2013 to December 2013 were retrospectively enrolled. Two independent chest radiologists analyzed the CT findings. Clinical, CT (stage, margin, pleural tag, axial location, and peritumoral interstitial thickening), and pathologic findings (stage, % lepidic growth, and LVI) were reviewed. Cox proportional hazard regression analysis was used to estimate the hazard ratios (HRs) for patients with (n = 34) and without (n = 241) recurrence.The κ index for agreement on the CT findings between radiologists was 0.705 to 0.845. In univariate analysis, % lepidic growth (P = 0.006), LVI (P < 0.001), size (P < 0.001), and staging (P = 0.011) differentiated significantly between patients with and without recurrence. Long diameter (P < 0.001), mass type (P < 0.001), marginal lobulation (P = 0.020), central location (P < 0.001), and peritumoral interstitial thickening (P < 0.001) were significantly related to recurrence on CT. Peritumoral interstitial thickening was positively correlated with tumor size (P < 0.001), LVI (P < 0.001), N staging (P = 0.005), stage (P < 0.001), mass type (P < 0.001), and recurrence (P = 0.003). In multivariate analysis, size (HR, 1.052; 95% CI, 1.022-1.082; P < 0.001), central location (HR, 3.152; 1.387-7.166; P = 0.006), and LVI (HR, 2.153, 95% CI, 1.038-4.465; P = 0.039) were independent predictors of recurrence.Large, centrally located tumors with LVI tend to recur after surgery. Presence of peritumoral interstitial thickening on CT appears to predict pathologic LVI and recurrence.

FIGURE 1

Flow diagram of the study patients (n = 275).

FIGURE 2

CT image obtained in a 69-year-old man with adenocarcinoma of the lung with recurrence in lung and bone after right upper lobectomy. (A, B) Thin-section axial CT lung images (1-mm thickness) obtained at the prevascular level. Images show a 32-mm sized peripheral lung mass (dotted lines, central imaginary line) with spiculated margin, peritumoral interstitial thickening (arrows), sun burst shape, in the right upper lobe, shown to be adenocarcinoma (acinar type). Right upper lobectomy was performed. (C) On histopathologic analysis, the tumor has extensive lymphovascular invasion (hematoxylin–eosin stain, original magnification ×100). The white box indicates the region in figure (D). (D) High power field image showing tumor cells (black arrowheads) invading a blood vessel (white arrows) (hematoxylin–eosin stain, original magnification ×400). The tumor was classified as pathologic T2a N1 M0. (E, F) Follow-up, thin-section axial CT lung image (1-mm thickness) obtained 15 mo after surgery, and axial CT bone image (5-mm thickness) obtained at the levels of the carina and right pulmonary artery, respectively. Images show newly developed small nodules (arrows) in the right lower lobe (E) and a soft tissue lesion involving the pleura (arrows) and causing destruction of the right 7th rib (asterisk) (F). CT = computed tomography.

FIGURE 3

CT image obtained in a 50-year-old man with adenocarcinoma of the lung with recurrence in lung and lymph nodes after left lower lobectomy. (A) Thin-section axial CT lung image (1-mm thickness) obtained at the level of the left lower lobar bronchus. Image shows a centrally located 43-mm tumor with peritumoral interstitial thickening (arrows) in the left lower lobe, shown to be a mucinous adenocarcinoma. Left lower lobectomy was performed. (B) The gross specimen is a yellowish mass (arrows) confined to the lung without pleural invasion but with pleural retraction. (C) On histopathologic analysis, the tumor has a spiculated margin with partly lepidic pattern (hematoxylin–eosin stain, original magnification ×12.5). The white box indicates the region shown in (D). (D) The interstitium of the lung is widened and thickened by tumor invasion (black arrowheads) and tumor cells are also evident in the lymphatics (white arrows) (hematoxylin–eosin stain, original magnification ×400). The tumor was classified as pathologic T2a N1 M0. Lymph node metastasis (4R) occurred after 15 mo despite surgery, and lung metastasis followed 20 mo after tumor resection (not shown). CT = computed tomography.

FIGURE 4

Graphs comparing the predictability of tumor recurrence in patients with and without recurrence on the basis of (A) peritumoral interstitial thickening (PIT) on CT (B) pathologic lymphovascular invasion (LVI) (C) axial location (central vs peripheral) and (D) nodule or mass type of the main tumor. Graphs were drawn with data from all patients with no missing data. All P values were <0.001. (+), positive, (−), negative, CT = computed tomography.