3D Specimen Mapping Expedites Frozen Section Diagnosis of Nonpalpable Ground Glass Opacities

Abstract

Background: Pulmonary ground glass opacities (GGOs) are early-stage adenocarcinoma spectrum lesions that are not easily palpable. Challenges in localizing GGOs during intraoperative pathology can lead to imprecise diagnoses and additional time under anesthesia. To improve localization of GGOs during frozen section diagnosis, we evaluated a novel technique, 3-dimensional near-infrared specimen mapping (3D-NSM).

Methods: Fifty-five patients with a cT1 GGO were enrolled and received a fluorescent tracer preoperatively. After resection, specimens were inspected to identify lesions. Palpable and nonpalpable nodules underwent 3D-NSM and the area of highest fluorescence was marked with a suture. Time for 3D-NSM, time for frozen section diagnosis, and number of tissue sections examined were recorded. To compare 3D-NSM with standard-of-care techniques, a control cohort of 20 subjects with identical inclusion criteria were enrolled. Specimens did not undergo 3D-NSM and were sent directly to pathology.

Results: 3D-NSM localized 54 of 55 lesions with 1 false negative. All 41 palpable lesions were identified by 3D-NSM. Thirteen (92.8%) of 14 nonpalpable lesions were located by 3D-NSM. Time to diagnosis for the 3D-NSM cohort was 23.5 minutes, compared with 26.0 minutes in the control cohort (P = .04). 3D-NSM did not affect time to diagnosis of palpable lesions (23.2 minutes vs 21.4 minutes; P = .10). 3D-NSM significantly reduced time to diagnosis for nonpalpable lesions (23.3 minutes vs 34.4 minutes; P < .0001). 3D-NSM also reduced the number of tissue sections analyzed in nonpalpable lesions (4.50 vs 11.00; P < .0001).

Conclusions: 3D-NSM accurately localizes GGOs and expedites intraoperative diagnosis by reducing the number of tissue sections analyzed for nonpalpable GGOs.

FIGURE 1

Three-dimensional near-infrared specimen mapping device. (A, B) The device consists of a light-free space for closed field fluorescence imaging. (C-H) Specimens are placed on a moving stage that allows image capture from a variety of viewing angles along 2 rotational axes.

FIGURE 2

Three-dimensional near-infrared specimen mapping (3D-NSM) localizes nonpalpable pulmonary lesions. This figure shows representative images from 2 patients with nonpalpable pulmonary lesions enrolled in the study. Preoperative computed tomography (CT) and positron emission tomography (PET) images are shown on the left with red arrows denoting lesions. The center panel shows brightfield images in which lesions cannot clearly be identified by visual inspection and palpation but are highly fluorescent on 3D-NSM.

FIGURE 3

Three-dimensional near-infrared specimen mapping (3D-NSM) fluorescence locates pulmonary ground glass opacities (GGOs). (A) Two by two tables comparing the accuracy of 3D-NSM in locating GGOs with the accuracy of finger palpation in locating GGOs. 3D-NSM had 1 false negative as compared with 14 false negatives by palpation. (B) Receiver-operating characteristic (ROC) curve evaluation for lesion mean fluorescence intensity. (C) denotes the mean fluorescence intensity of lesions and the background tissue when stratified by palpability. The mean fluorescence intensities of both palpable and nonpalpable GGOs were significantly higher than background tissue. (D) The signal-to-background ratios of nonpalpable lesions as compared with palpable lesions. (E) The signal-to-background ratios of all lesions when stratified by histopathological diagnosis. ***P < .0001.

FIGURE 4

Correlation of macroscopic fluorescence with folate receptor alpha (FRα) expression in lung lesions. This figure shows representative images of patients in the study that underwent 3-dimensional near-infrared specimen mapping (3D-NSM). The leftmost 2 columns show macroscopic brightfield and 3D-NSM images, respectively. The center column shows microscopic evaluation of the specimens after hematoxylin and eosin staining. The rightmost 3 columns show immunohistochemistry analysis for FRα expression and fluorescence microscopy, showing clear correlation between the areas of highest FRα expression and brightest fluorescence. (H&E, hematoxylin and eosin.)

FIGURE 5

Three-dimensional near-infrared specimen mapping (3D-NSM) expedites time to frozen section diagnosis of nonpalpable lesions. (A) Time to frozen section diagnosis, comparing 3D-NSM-guided pathology with the control cohort undergoing standard frozen section. When stratified by lesion palpability, 3D-NSM significantly reduced time to diagnosis for nonpalpable lesions but did not affect time to diagnosis of palpable lesions. (B) The correlation of number of tissue sections performed with the time to frozen section diagnosis, showing a strong positive correlation with R = 0.7064. (C) The number of tissue sections cut per specimen, comparing 3D-NSM–guided pathology with the control cohort undergoing standard frozen section. When stratified by lesion palpability, 3D-NSM significantly reduced the number of specimen sections taken, suggesting that this is the mechanism by which 3D-NSM expedites frozen section diagnosis of nonpalpable lesions. ***P < .0001. (Ctrl, control.)