Manejo de las Opacidades en Vidrio Esmerilado Patricia Vujacich Hospital de Clínicas. José de San Martín UBA

Ningún conflicto de intereses para declarar

Qué hacer con una opacidad en vidrio esmerilado (OVE-GGO)

OVE-GGO Causas Infecciosas COP Fibrosis focal no específica Trauma Espectro lesiones premalignas-adenoCa

Mixto GGO-OVE con componente sólido Opacidad en vidrio esmerilado (OVE-GGO): área de incremento brumoso de la opacidad pulmonar, a través de la cual se pueden ver las estructuras broncovasculares. OVE Focal (nódulo no sólido): áreas nodulares focales de aumento de la atenuación del parénquima a través del cual se pueden definir estructuras broncovasculares y septos. Puros GGO-OVE Mixto GGO-OVE con componente sólido Ca Bronquioloalveolar temprano (BAC) Hiperplasia adenomatosa atípica (AAH) Adenocarcinoma (AdenoCa)

2011 Nueva clasificación de adenocarcinoma de pulmón

“El esqueleto de esta clasificación es patológica” “El diagnóstico del carcinoma de pulmón es un proceso multidisciplinario que requiere correlación con información clínica, radiológica, molecular y quirúrgica”

Noguchi M, Morikawa A, Kawasaki M, et al Noguchi M, Morikawa A, Kawasaki M, et al. Small adenocarcinoma of the lung: histologic characteristics and prognosis. Cancer 1995; 75:2844–2852.

Noguchi M, Morikawa A, Kawasaki M, et al Noguchi M, Morikawa A, Kawasaki M, et al. Small adenocarcinoma of the lung: histologic characteristics and prognosis. Cancer 1995; 75:2844–2852.

¿Como distinguir a las OVE no evolutivas, benignas de aquellas asociadas a malignidad ? ¿Como llegar a un diagnóstico definitivo en corto plazo?

Tamaño No sirve de mucho… Si bien > o < 5-10 mm Nódulos benignos grandes Sirve más que nada para “esperar un lento crecimiento”… Eur J Radiol 2011 Mar;77(3):410-6. Felix et al. et al CT characteristics of resolving ground-glass opacities in a lung cancer screening programme. J Thorac Oncolo 2006 Nov;1(9 Suppl):S20-6. Radiographic imaging of bronchioloalveolar carcinoma: screening, patterns of presentation and response assessment.

Persistent pure ground-glass opacity lung nodules ≥ 10 mm in diameter at CT scan: histopathologic comparisons and prognostic implications Estudio sobre cohorte de 46 ggo puros resecados seguidos durante ≥ 3 años Correlacion entre características que podrían predecir invasión (Adeno CA invasor) vs AIS o MIA 19 AISs (41%), 9 MIAs (20%), y 18 invasivo adenocarcinomas (39%). En análisis univariado Broncograma aéreo (P = .012), Tamaño del nódulo (P = .032, cutoff = 16.4 mm in diameter) Masa del nódulo (P = .040, cutoff = 0.472 g) En análisis multivariado Tamaño (P = .010) Masa del nódulo (P = .016) Fueron factores determinantes de Adeno Ca Invasor No hubo recurrencias en ≥ 3 años EN GGO PERSITENTES EL TAMAÑO Y LA MASA DEL NODULO FUERON DETERMINANTES DE ADENOCA INVASOR Lim HJ et al. CHEST 2013 Oct, 144 1291-9

Forma Li F, et al. Malignant vs benign nodules at CT screening for lung cancer: comparison of thin-section CT findings. Radiology 2004; 233: 793–798.

Forma y crecimiento La forma de las OVE maligna tendió a ser redondeada, oval o lobulada (no poligonal) (p=0.006). Las OVE que resolvieron fueron significativamente más lobuladas (p= 0.006), poligonales en forma (p = 0.02), mixtas (p= 0.003) y mayores (p < 0.0001) que las OVE que no se resolvieron fr Eur J Radiol 2011 Mar;77(3):410-6. Felix et al. et al CT characteristics of resolving ground-glass opacities in a lung cancer screening programme.

El crecimiento radial aparente estuvo asociado a OVE neoplásica (p=0 El crecimiento radial aparente estuvo asociado a OVE neoplásica (p=0.010); de todas formas, en 7 (27%) de 26 casos fue observado en una lesión benigna Los márgenes bien definidos se asociaron significativamente a histología maligna (p=0.003), aunque también se observo en lesiones benignas. Infante et al

Crecimiento Desvanecimiento Softwares volumétricos J Comput Assist Tomogr 2008 Sep-Oct;32(5):792-8.

Cuándo es más posible que un nódulo crezca? Cuando el tamaño inicial es mayor Cuando el paciente es fumador Cuando tenga ≥ -670HU de atenuación

The association between baseline clinical-radiological characteristics and growth of pulmonary nodules with ground- glass opacities Características clínicas y radiológicas de crecimiento Estudio retrospectivo de pacientes con nódulos pulmonares (1) lesion diameter of ≤3 cm, (2) GGO proportion of ≥50%, (3) observación sin tratamiento por 6 meses previos. 120 nódulos en 67 pacientes. 2 endpoints, “Tiempo para crecer 2 mm” e “incidencia de crecimiento 2-mm “ Riesgo proporcional de Cox y modelo de regresión logística Tiempo de observación 4.2 años, 34 lesiones crecieron Hazard ratio (HR) para tabaquismo fue 3.67 (P<0.01). Compared with those ≤1 cm, HRs for 1.1-2 cm and 2.1-3 cm lesions were 2.23 (P=0.08) and 5.08 (P=0.04), respectively. Odds ratio (OR) for smoking history was 6.51 (P<0.01); OR for lesion diameter of 1.1-3 cm (versus ≤1 cm) was 4.06 (P=0.02). HISTORIA DE TABAQUISMO Y DIAMETRO INICIAL DE LA LESION SE ASOCIAN FUERTEMENTE CON CRECIMIENTO. Kobarashi Y et al. Lung Cancer. 2014 Jan;83(1):61-64

Computed tomography attenuation predicts the growth of pure ground-glass nodules Estudio retrospectivo de 124 casos de GGO puros. Seguimiento 2 años 64 crecieron Analisis inivariado reveló diferencias significativas entre la ATENUACION TOMOGRAFICA entre los que crecieron y los que no (-602.9 ± 90.7 Hounsfield units [HU] vs -705.7 ± 77.7HU, P < 0.0001). Si la densidad era de ≥ -670HU (n = 62; 93.2%) las lesiones crecieron para lesiones con menor densidad < -670HU (n = 62; 31.6%; P < 0.0001). SENSIBILIDAD 78.1% ESPECIFICIDAD 80.0%, EL VALOR DE LA ATENUACION medido por TAC puede ser útil en predecir CRECIMIENTO DE GGO Eguchi T et al. Lung Cancer. 2014 Jun;84(3):242-7

Componente sólido Una densidad central o excéntrica (OVE mixto) se asocio con malignidad en 75% de los casos, pero globalmente la asociación entre un componente sólido y Ca de pulmón no fue significativa (p=0.27). Tipo mixto se asoció con adenocarcinoma invasor. Broncograma aéreo, pseudocavitación, linfangitis. GGO mixto se asoció con malignidad Clin Imaging 2002 Mar-Apr;26(2):95-100. Bronchioloalveolar carcinoma and adenocarcinoma with bronchioloalveolar features presenting as ground-glass opacities on CT. Henschke C Korean J Radiol. 2007 Jan-Feb;8(1):22-31. Nodular ground-glass opacities on thin-section CT: size change during follow-up and pathological results.

Correlation between the size of the solid component on thin- section CT and the invasive component on pathology in small lung adenocarcinomas manifesting as ground-glass nodules. 58 nódulo subsólidos Diámetros máximos del nódulo y del componente sólido medidos por 2 radiólogos en 3D) y 2D) planos. Los diámetros máximos del tumor y su componente invasivo medidos por 2 patóliogos. Comparación de TC con medición de patología ALTA CORRELACION entre el tamaño del componente sólido y el componente invasivo, Correlación entre tamaño total del nódulo y el tamaño del tumor (r = 0.82-0.87 for 3D measurement, 0.72-0.88 for 2D measurement; p < 0.0001). El tamaño del nódulo subsólido en 3D y 2D fue significativamente mayor que el diámetro del tumor (p < 0.0001). En cuanto al componente sólido fue mayor en 3D que el componente invasivo En 2D fue similar. Tomando límite de corte 3 mm para el componente sólido CIS y MIA fueron predichos con una especificiidada del 100% (28 of 28). CORRELACION SIGNIFICATIVA ENTRE TAMAÑO DEL COMPONENTE SOLIDO EN LA TAC CON EL COMPONENTE INVASIVO EN LA PATOLOGIA. J Thorac Oncol. 2014 Jan;9(1):74-82

Zhonghua Yi Xue Za Zhi. 2014 Apr 8;94(13):1010-3. [Diagnostic value of solid component for lung adenocarcinoma shown as ground-glass nodule on computed tomography]. [Article in Chinese] Ge X1, Gao F, Li M, Chen Y, Lü F, Ren Q, Hua Y2. Author information Abstract OBJECTIVE: To explore the feasibility of making a preoperative diagnosis of lung adenocarcinoma shown as ground-glass nodule(GGN) on computed tomography (CT). METHODS: A total of 143 GGN lesions proved pathologically were divided randomly into A and B groups. Then each group was further divided pathologically into preinvasive lesion, minimal invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) subgroups. Group A (n = 101), size of lesion, proportion of ground glass opacity (GGO) composition of lesion, long diameter, longest diameter and size of solid component in lesion were measured on CT so as to establish the CT diagnostic standard of lung adenocarcinoma shown as GGN on CT. Group B (n = 42) was employed to evaluate the accuracy of the above CT diagnostic standard. SPSS 17.0 software was used for statistical analysis. RESULTS: Significant statistic significance existed in all parameters among all groups (P < 0.05). All parameters were correlated the pathologic type of lesion. The differences were statistically significant (P = 0.000). Through the receiver operating characteristic (ROC) curve, between groups of preinvasive lesion and MIA, each parameter had a medium diagnostic value of 0.70-0.90; between groups of MIA and IAC, size of lesion and long diameter of solid component in lesion had a medium diagnostic value of 0.70-0.90, longest diameter of solid component, size of solid component in lesion and proportion of GGO composition of lesion had a high diagnostic value with an AUC of >0.90. The CT diagnostic standard, derived from group A, was used to analyze the pathologic type of group B. And t no significant statistic significance existed between CT preoperative diagnosis and operative pathologic diagnosis (P > 0.05) . The correct diagnosis rates of size of lesion, proportion of GGO composition of lesion, long diameter, longest diameter and size of solid component in lesion were 71.43%, 76.19%, 90.05%, 90.05% and 88.10% respectively. CONCLUSION: Based upon size of lesion, proportion of GGO composition of lesion, long diameter, longest diameter and size of solid component in lesion, preoperative CT examination may be used to determine the pathological types of lung adenocarcinoma shown as GGN

PLoS One. 2014 Aug 7;9(8):e104066. doi: 10.1371/journal.pone.0104066. eCollection 2014. Quantitative CT analysis of pulmonary ground-glass opacity nodules for the distinction of invasive adenocarcinoma from pre-invasive or minimally invasive adenocarcinoma. Son JY1, Lee HY1, Lee KS1, Kim JH1, Han J2, Jeong JY2, Kwon OJ3, Shim YM4. Author information Abstract OBJECTIVES: We aimed to analyze the CT findings of ground-glass opacity nodules diagnosed pathologically as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma in order to investigate whether quantitative CT parameters enable distinction of invasive adenocarcinoma from pre-invasive or minimally invasive adenocarcinoma. METHODS: We reviewed CT images and pathologic specimens from 191 resected ground-glass opacity nodules with little or no solid component at CT. Nodule size, volume, density, mass, skewness/kurtosis, and CT attenuation values at the 2.5th-97.5th percentiles on histogram, and texture parameters (uniformity and entropy) were assessed from CT datasets. RESULTS: Of 191 tumors, 38 were AISs (20%), 61 were MIAs (32%), and 92 (48%) were invasive adenocarcinomas. Multivariate logistic regression analysis helped identify the 75th percentile CT attenuation value (P = 0.04) and entropy (P<0.01) as independent predictors for invasive adenocarcinoma, with an area under the receiver operating characteristic curve of 0.780. CONCLUSION: Quantitative analysis of preoperative CT imaging metrics can help distinguish invasive adenocarcinoma from pre-invasive or minimally invasive adenocarcinoma.

PLoS One. 2014 Aug 7;9(8) Quantitative CT analysis of pulmonary ground-glass opacity nodules for the distinction of invasive adenocarcinoma from pre-invasive or minimally invasive adenocarcinoma.

Rol del PET TC No útil si < 8-10 mm PET falsos negativos en lesiones Tipo a 100% Tipo b 80% Tipo c 47% PET verdaderos positivos Tipo d- e- f 70-100%

Biopsias Punción bajo TAC rédito en menos de 2 cm 64.6% Si vidrio esmerilado >50% 51% Si vidrio esmerilado <50% 75% Si sólo vidrio esmerilado 32% Biopsia core *concordancia 73% con biopsia Q. 25% falsos neg Biopsia quirúrgica Lung Cancer 2006 Feb;51(2):173-9. Shimizu K et al Percutaneous CT-guided fine needle aspiration for lung cancer smaller than 2 cm and revealed by ground-glass opacity at CT. *Kim TJ, et al. Diagnostic accuracy of Ctguided core biopsy of ground-glass opacity pulmonary lesions. AJR Am J Roentgenol 2008; 190: 234–239

El manejo óptimo está en evolución con el desarrollo de nuevas tecnologías. No hay certeza de riesgo del diagnóstico tardío tiempo óptimo de duración del seguimiento para las OVE y semisólidas Rol de las imágenes volumétricas Tecnologías broncoscópicas avanzadas Resecciones quirúrgicas limitadas Cálculo del costo-efectividad de las diferentes estrategias. Am J Respir Crit Care Med.. 2012 Feb 15;185(4):363-72.. Decision making in patients with pulmonary nodules. Ost DE.

Dante trial Mild trial IELCAP IALSC Larga sobrevida en GGO J Thorac Oncol. 2012 Oct;7(10):1541-6. Long-term surveillance of ground-glass nodules: evidence from the MILD trial. Silva M, Sverzellati N, Manna C, Negrini G, Marchianò A, Zompatori M, Rossi C, Pastorino U

Usar técnicas TAC sin contraste con cortes finos en el seguimiento de estos nódulos Si desarrollan un componente sólido son frecuentemente malignos y requieren evaluación Si miden >10 mm seguimiento cada 3 meses y eventual biopsia Límite o no evaluación en individuos con comorbilidades que limiten espectativa de vida

Usar técnicas TAC sin contraste con cortes finos en el seguimiento de estos nódulos Si miden >10 mm seguimiento cada 3 meses y/o considerar resección Límite o no evaluación en individuos con comorbilidades que limiten espectativa de vida

PET no uso para evaluar parte sólida de lesiones con c. sólido ≤ 8 mm Se puede usar biopsia no quirúrgica para diagnóstico y/o combinarse con marcación con cualquier técnica que facilite resección Nódulos cuya parte sólida >15 mm proceder a evaluación con PET y biopsia no quirúrgica y/o resección

Y qué pasa en el seguimiento de pacientes con más de un nódulo?

Y si tienen o han tenido cancer en medio de un seguimiento? Múltiples estudios no controlados mostraron benignidad en la gran mayoría de nódulos de 4 - 12 mm (>85%) (datos de más de 400 ggo en 25 ptes- 23 ptes; 1 y 2 BAC) Pensar en lento crecimiento y espectativa de vida NO debe negarse tratamiento a menos que se haya comprobado metástasis histológicamente Multiple focal pure ground-glass opacities on HRCT images: clinical significance in patients with lung cancer. Xiao J AJR Am J Roentgenolo 2010 Aug;195(2) Multiple focal pure ground-glass opacities on high-resolution CT images: Clinical significance in patients with lung cancer.

Y si tienen o han tenido cancer extrapulmonar? 59 opacidades en 28 ptes 68% malignas Diferencias en el tamaño, proporción del componente sólido proporción, márgenes y “burbuja”, broncograma aéreo o retracción pleural (p< 0.05) Chest 2008 Jun;133(6):1402-9. Pulmonary nodular ground-glass opacities in patients with extrapulmonary cancers: what is their clinical significance and how can we determine whether they are malignant or benign lesions?

Y por cuánto tiempo el seguimiento? How long should small lung lesions of ground- glass opacity be followed? GGO menores de 3 cm Proporción de vidrio esmerilado >50% Observación por más de 6 meses previos. 108 nódulos 69 menos de 1 cm Período de observación medio 4.2 años 29 lesiones crecieron Crecimiento medio 7 mm (2-32) Todos los tumores comenzaron a crecer en 3 años, la mayoría en los 2 primeros años Los autores concluyen que estas lesiones deben seguirse al menos 3 años.

Y por cuánto tiempo el seguimiento? Largo seguimiento… Retrospectivo…

Cuando se clasificaron los nódulos en cuatro grupos de acuerdo al tamaño inicial (<5 mm, 5-7 mm, 8-9 mm, y >10 mm), se observo una tendencia significativa de crecimiento en relación a los de mayor tamaño (p = 0,003). El desarrollo de una nueva porción sólida interna se asoció con un crecimiento significativo del GGO nódulo (P =0.009). El tiempo de duplicación del volumen de los 12 nódulos fue de 769 días (rango, 330-3031 días).

No es necesaria la disección de ganglios mediastinales en resección completa de ggo Surgical management of pulmonary adenocarcinoma presenting as a pure ground-glass nodules 1267 patients with pulmonary adenocarcinoma, 48 GGN puros en 42 exploración mediastinal disección y muestreo ( media 23 ganglios) Resecciones limitadas en la tercera parte de pacientes NINGUN GANGLIO POSITIVO Media de seguimiento post op 39 meses (23-79) Recurrencia de ggo 6 (12.5%) . CONCLUSIONeS: Resecciones limitadas seguras… sobre todo por la posibilidad alta de lesiones múltiples. Ningún beneficio en explorar mediastino Sim HJ et al. Eur J Cardiothorac Surg. 2014 Feb 23

Y qué pasa si no los operamos? Outcomes of unresected ground-glass nodules with cytology suspicious for adenocarcinoma. 63 pacientes sin historia previa de adenoCA que se hicieron PPA con citología positiva para adeno CA entre January 2002 y December 2011. Compararos la evolución de aquellos que se resecaron vs aquellos que decidieron observación. 47 resecados 16 observacion 6 (37.5%) crecieron o incrementó parte sólida (5 Cx o radiación). No hubo metástasis ni muertes en el grupo observación 2 metástasis, 5 nuevos cánceres en le pulmón remanente y 3 progresión de GGO GGO observadas luego de la biopsia no demostraron incremento en metástasis o muerte reacionada al cancer. Retraso en la toma de decision quirurgica no afecto pronóstico J Thorac Oncol. 2014 May;9(5):685-91

J Thorac Oncol. 2014 May;9(5):685-91. doi: 10. 1097/JTO Gulati CM1, Schreiner AM, Libby DM, Port JL, Altorki NK, Gelbman BD. Abstract BACKGROUND: Five-year survival rates for resected stage I adenocarcinoma approach 100%. Given previous studies describing the prolonged indolent natural history of ground-glass lesions suspicious for early adenocarcinoma, our purpose in this study was to determine if outcomes were different among patients who were observed for radiographic and biopsy suspected early adenocarcinoma compared with those who were resected immediately. METHODS:We identified 63 patients with no prior history of lung adenocarcinoma who had undergone computer tomography-guided fine-needle aspiration of ground-glass opacities with cytology concerning for new early adenocarcinoma between January 2002 and December 2011. We compared the clinical outcomes of patients who were resected after abnormal cytology results and those who opted for watchful waiting. RESULTS: Sixteen patients elected to observe their ground-glass nodules despite having suspicious cytology results, whereas 47 opted for immediate resection. Of the 16 observed patients, six (37.5%) ultimately demonstrated growth or increase solid component of the ground-glass nodule. Five of these patients elected for definitive therapy by surgical resection or radiation. There were no occurrences of distant metastasis or lung cancer-associated deaths in the observed group. Of the 47 resected patients, two developed metastatic disease, five developed new cancers in remaining lung, and three developed progression in existing ground-glass nodules. CONCLUSIONS: Ground-glass lesions that were observed after biopsy did not demonstrate any increased rates of metastasis or cancer-related deaths and delayed resection does not seem to have a negative effect on outcomes

Gracias por su atención…

Small adenocarcinoma of the lung Small adenocarcinoma of the lung. Histologic characteristics and prognosis. Noguchi M, Morikawa A, Kawasaki M, Matsuno Y, Yamada T, Hirohashi S, Kondo H, ShimosaCancer. 1995 Jun 15;75(12):2844-52. to Y. Source Pathology Division, National Cancer Center Research Institute, Tokyo, Japan. Abstract BACKGROUND: Although there are many reported prognostic indicators for pulmonary adenocarcinoma, the clinicopathologic characteristics and prognostic factors of early stage adenocarcinoma have not been evaluated fully, except for several studies of nonmucinous and sclerosing bronchioloalveolar carcinoma. METHOD: Two hundred thirty-six surgically resected small peripheral adenocarcinomas measuring 2 cm or less in greatest dimension were reviewed using a simple histologic classification of six types based on tumor growth patterns. RESULTS: Type A (localized bronchioloalveolar carcinoma [LBAC]) (n = 14) revealed replacement growth of alveolar-lining epithelial cells with a relatively thin stroma. In type B (LBAC with foci of structural collapse of alveoli) (n = 14), fibrotic foci due to alveolar collapse were observed in tumors of LBAC. Type C (LBAC with foci of active fibroblastic proliferation) (n = 141) was the largest group in this study, and foci of active fibroblastic proliferation were evident. Type D (poorly differentiated adenocarcinoma), type E (tubular adenocarcinoma) and type F (papillary adenocarcinoma with a compressive growth pattern) (n = 61) showed compressive and expanding growth. Types A and B showed no lymph node metastasis and the most favorable prognosis (100% 5-year survival) of the six types. CONCLUSION: Histologic types A and B are thought to be in situ peripheral adenocarcinoma, whereas type C appears to be an advanced stage of types A and B. Conversely, types D, E, and F are small advanced adenocarcinomas with a less favorable prognosis.

Multiple focal pure ground-glass opacities on HRCT images: clinical significance in patients with lung cancer]. [Article in Chinese] Xiao J, Wu Y, Xu L, Huang Y, Liu Y. Source Department of Radioligy, Affiliated Hospital of Shandong Academy of Medical Sciences, Ji'nan 250031, China. Abstract BACKGROUND AND OBJECTIVE: Some cases of lung cancer in addition to a primary tumor are associated with multiple pure ground-glass opacities (pGGOs). The objective of this study is to evaluate the clinical significance of multiple pGGOs on CT images of patients with lung cancer. The number, size, distribution, and morphological characteristics of the pGGOs were evaluated. Serial changes in pGGOs that were not surgically resected were analyzed at follow-up CT. METHODS: The cases of 25 patients with proven lung cancer and associated multiple pGGOs on CT images were retrospectively reviewed. RESULTS: In total, 207 pGGOs were detected. The size of the opacities ranged from 2 mm to 31 mm in largest diameter. Lung cancer and pGGOs were seen in the same lobe and/or in other lobes. Of the lesions, 183 (88.4%) had a round shape or well-defined border. Histological findings were obtained for 17 lesions representing 87 pGGOs that were surgically resected, namely, 13 atypical adenomatous hyperplasias, 3 bronchioloalveolar carcinomas, and 1 focal fibrosis. Of the 120 pGGOs followed up with CT for a median duration of 61.5 months, 113 (94.2%) retained their size, 1 decreased in size, and 6 disappeared. CONCLUSIONS: The size of most pGGOs associated with lung cancer did not change during the follow-up period. Most of the lesions histologically diagnosed were atypical adenomatous hyperplasias or bronchioloalveolar carcinomas. The results justify the therapeutic strategy of resecting the primary tumor without therapeutic intervention in the remaining pGGOs.

AJR Am J Roentgenol. 2010 Aug;195(2) Multiple focal pure ground-glass opacities on high-resolution CT images: Clinical significance in patients with lung cancer. Tsutsui S, Ashizawa K, Minami K, Tagawa T, Nagayasu T, Hayashi T, Uetani M. Source Nagasaki University Graduate School of Biomedical Sciences, Japan. Abstract OBJECTIVE: The purpose of this study was to evaluate the clinical significance of multiple focal pure ground-glass opacities (GGOs) on high-resolution CT images of patients with lung cancer. MATERIALS AND METHODS: The cases of 23 patients with proven lung cancer and associated multiple focal pure GGOs on high-resolution CT images were retrospectively reviewed. The number, size, distribution, and morphologic characteristics of focal pure GGOs were evaluated. Serial changes in focal pure GGOs that were not surgically resected were analyzed at follow-up high-resolution CT. RESULTS: The number of focal pure GGOs was 196 in total. The size of the opacities ranged from 2 to 30 mm in largest diameter. Lung cancer and focal pure GGOs were seen in the same lobe and/or in the other lobes. One hundred seventy-one of the lesions (87%) had a well- defined border or round shape. Histologic findings were obtained for 15 lesions representing 74 focal pure GGOs that were surgically resected: 11 atypical adenomatous hyperplasia lesions, three bronchioloalveolar carcinomas, and one lesion of focal fibrosis. In 110 of the cases of focal pure GGOs, all of which were followed up with HRCT for a median duration of 1,351 days, the size of 105 lesions (95%) did not change, the size of one decreased, and four lesions disappeared. CONCLUSION: The size of most focal pure GGOs associated with lung cancer did not change during the follow-up period. Most of the small number of lesions histologically diagnosed were atypical adenomatous hyperplasia or bronchioloalveolar carcinoma. These data justify the therapeutic strategy of resecting the primary tumor without therapeutic intervention in the remaining focal pure GGOs.

Eur J Radiol. 2011 Mar;77(3):410-6. CT characteristics of resolving ground-glass opacities in a lung cancer screening programme. Felix L, Serra-Tosio G, Lantuejoul S, Timsit JF, Moro-Sibilot D, Brambilla C, Ferretti GR. Source Clinique Universitaire de Radiologie et Imagerie Médicale, Université Grenoble I, CHU Grenoble, France. Abstract PURPOSE: This study aimed at evaluating the computed tomography (CT) characteristics of resolving localized ground-glass opacities (GGOs) in a screening programme for lung cancer. MATERIAL AND METHODS: 280 patients at high-risk for lung cancer (221 men, 59 women; mean age, 58.6 years), divided into four groups (lung cancer history (n = 83), head and neck cancer history (n = 63), symptomatic (n = 88) and asymptomatic (n = 46) cigarette smokers), were included in a prospective trial with annual low-dose CT for lung cancer screening. We retrospectively reviewed all localized GGOs, analyzed the CT characteristics on initial CT scans and changes during follow-up (median 29.1 months). Variables associated with resolution of GGOs were tested using chi-square or Mann-Whitney tests. RESULTS: A total of 75 GGOs were detected in 37 patients; 54.7% were present at baseline and 45.3% appeared on annual CT. During follow-up, 56.2% persisted and 43.8% disappeared. The resolving localized GGOs were significantly more often lobular GGOs (p = 0.006), polygonal in shape (p = 0.02), mixed (p = 0.003) and larger (p < 0.0001) than non- resolving localized GGOs. CONCLUSION: Localized GGOs are frequent and many disappeared on follow-up. CT characteristics of resolving GGOs show significant differences compared to persistent ones. This study emphasizes the importance of short-term CT follow-up in subjects with localized GGOs.

Clin Imaging. 2002 Mar-Apr;26(2):95-100. Bronchioloalveolar carcinoma and adenocarcinoma with bronchioloalveolar features presenting as ground-glass opacities on CT. Mirtcheva RM, Vazquez M, Yankelevitz DF, Henschke CI. Source Department of Radiology, New York Presbyterian Hospital-Weill Cornell Medical Center, 525 East 68th Street, New York, NY 10021, USA. Abstract OBJECTIVE: As bronchioloalveolar carcinoma (BAC) is noninvasive but, in its later stages, has a worse prognosis than adenocarcinoma with bronchioloalveolar features (ACB), early identification and differentiation is important for therapeutic and prognostic purposes. We wanted to identify features of BAC, which differentiated it from ACB when both presented as ground-glass opacities (GGOs) on CT. MATERIALS AND METHODS: We reviewed all pathologic specimens of patients who were diagnosed with BAC and ACB in the lung from 1991 to 1999 in our institution and whose malignancy presented as a GGO on CT. This yielded 29 patients, 15 with BAC and 14 with ACB with GGOs on CT. Both univariate frequency table and multivariate logistic regression approaches were used to analyze the CT characteristics of these GGOs (location, GGO pattern, size, shape, margin, presence and type of air bronchogram and pseudocavitation). RESULTS: BAC most frequently had a "GGO halo" around a solid opacity, often was a GGO "mixed with consolidation" with the smallest BACs being "pure GGO." Air bronchograms were frequently present in the largest GGOs. Pseudocavitations were rare. ACB, on the other hand, most frequently presented as a GGO "mixed with consolidation," less frequently with a "GGO halo" and rarely with "superimposed lymphangitis." The air bronchograms, frequently present, were usually tortuous and ectatic. Pseudocavitation was present in about one-third of the cases. The most useful CT features of GGO in separating those due to BAC from those due to ACB were pure (uniform) ground-glass attenuation and absence of lymphangitis. CONCLUSION: The CT features of BAC and ACB presenting as GGO reflect the histologic descriptions of these carcinomas

Lung Cancer. 2006 Feb;51(2):173-9. Percutaneous CT-guided fine needle aspiration for lung cancer smaller than 2 cm and revealed by ground-glass opacity at CT. Shimizu K, Ikeda N, Tsuboi M, Hirano T, Kato H. Source First Department of Surgery, Tokyo Medical University, Nishishinjyuku, Shinjyuku-ku, Japan. shimizuk@hiroshima-u.ac.jp Abstract The purpose of this retrospective study was to evaluate the value of preoperative percutaneous CT-guided fine needle aspiration biopsy (CTNB) for peripheral lung cancers less than 2 cm in size, especially in cases showing of ground-glass opacities (GGO). From 1999 to 2002, 151 small lung cancers were resected in Tokyo Medical University Hospital. Among them, 96 patients (63.6%) in whom the lesions were located in the outer half of the lung field underwent CTNB in order to obtain a preoperative diagnosis. The factors influencing the diagnostic yield were analyzed. The overall diagnostic yield of CTNB was 64.6%: 48.5% for lesions smaller than 10 mm, 62.5% for those 11- 15 mm, and 83.9% for those 16-20 mm, respectively. The diagnostic yield in GGO-dominant lesions (GGO ratio < 50%) and solid-dominant lesions (GGO ratio < 50%) were 51.2% and 75.6% (p = 0.018). In the GGO-dominant group, the diagnostic yields were 35.2% for lesions smaller than 10 mm, 50.0% for those 11-15 mm, and 80.0% for those 16-20 mm. In the solid- dominant group, diagnostic yield was 62.5% for cases smaller than 10 mm, 75% for 11-15 mm and 85.7% for 16-20 mm, respectively. Satisfactory diagnostic yield (>80%) was obtained by CTNB in cases larger than 15 mm. CTNB is a useful diagnostic modality for peripheral small lung cancers; however, for GGO-dominant lesions, the preoperative diagnostic yield is not significantly better than for solid-dominant lesions

Thorac Surg Clin. 2007 May;17(2):191-201, viii. Management of the peripheral small ground-glass opacities. Yoshida J. Source Division of Thoracic Surgery, Department of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. jyoshida@east.ncc.go.jp Abstract Pure ground-glass opacities (GGO) with a small consolidation area are mostly bronchioloalveolar carcinomas that have not yet become invasive, whereas a minority represents only inflammatory changes. Even if they are cancers, they are slow- growing and often remain unchanged for several years. There is no need for immediate resection of GGO lesions and a watchful waiting strategy is recommended. It seems that a lower-impact surgery (eg, wedge resection or segmentectomy) is curative for these lung cancers. Because high-resolution CT seems to predict noninvasive or minimally invasive GGO lung cancers with high reliability, less invasive treatments like radiofrequency ablation have greater appeal

J Thorac Oncol. 2006 Nov;1(9 Suppl):S20-6. Radiographic imaging of bronchioloalveolar carcinoma: screening, patterns of presentation and response assessment. Gandara DR, Aberle D, Lau D, Jett J, Akhurst T, Heelan R, Mulshine J, Berg C, Patz EF Jr. Source University of California Davis Cancer Center, Sacramento, CA, USA. david.gandara@ucdmc.ucdavis.edu Erratum in J Thorac Oncol. 2007 Jan;2(1):11. Heelan, Robert [added]. Abstract Bronchioloalveolar carcinoma (BAC) is a previously uncommon subset of adenocarcinoma with unique epidemiology, pathology, radiographic presentation, clinical features, and natural history compared with other non-small cell lung cancer (NSCLC) subtypes. Classically, BAC demonstrates a relatively slow growth pattern and indolent clinical course. However, in a subset of patients, rapid growth and death from bilateral diffuse consolidative disease occurs within months of diagnosis or recurrence. Recent data suggest that the incidence of BAC is increasing, notably in younger nonsmoking women. The initial radiographic presentation of BAC varies considerably, from single ground glass opacities (GGOs) or nodules of mixed ground glass and solid attenuation to diffuse consolidative or bilateral multinodular disease. The rising incidence of BAC is also reflected in recent lung cancer screening studies employing helical computed tomography (CT), where the differential diagnosis of GGOs includes not only BAC and overt adenocarcinoma, but inflammatory disease, focal fibrosis, and atypical adenomatous hyperplasia. Because advanced-stage BAC presents as measurable mass lesions in fewer than 50% of cases, determination of radiographic response to therapy by standard criteria is often difficult. Here, we review current data regarding the radiographic imaging of BAC: its radiographic presentations in asymptomatic early-stage and in advanced-stage disease, the functional imaging characteristics of BAC, and challenges of response assessment, including evolving opportunities for computer-assisted image analysis

Korean J Radiol. 2007 Jan-Feb;8(1):22-31. Nodular ground-glass opacities on thin-section CT: size change during follow-up and pathological results. Lee HJ, Goo JM, Lee CH, Yoo CG, Kim YT, Im JG. Source Department of Radiology, University College of Medicine and Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul 110-744, Korea. Abstract OBJECTIVE: To evaluate the inter-group differences in growth and the pathological results of nodular ground-glass opacities (GGOs) according to their size and focal solid portions. MATERIALS AND METHODS: Ninety-six nodular GGOs in 55 individuals followed by CT for at least one month from an initial chest CT were included. Forty nodular GGOs in 30 individuals were pathologically confirmed to be: adenocarcinoma (n = 15), bronchioloalveolar carcinoma (BAC) (n = 11), atypical adenomatous hyperplasia (AAH) (n = 8), focal interstitial fibrosis (n = 5) and aspergillosis (n = 1). Lesions were categorized based on high-resolution CT findings: pure nodular GGO (PNGGO) < or = 10 mm, PNGGO > 10 mm, mixed nodular GGO (MNGGO) < or = 10 mm, and MNGGO > 10 mm. In each group, the change in size during the follow-up period, the pathological results and the rate of malignancy were evaluated. RESULTS: Three MNGGO lesions, and none of the PNGGO, grew during the follow-up period. Resected PNGGOs < or = 10 mm were AAH (n = 6), BAC (n = 5), and focal interstitial fibrosis (n = 1). Resected PNGGOs > 10 mm were focal interstitial fibrosis (n = 4), AAH (n = 2), BAC (n = 2), and adenocarcinoma (n = 2). Resected MNGGOs < or = 10 mm were adenocarcinoma (n = 2), and BAC (n = 1). Resected MNGGOs > 10 mm were adenocarcinoma (n = 11), BAC (n = 3), and aspergillosis (n = 1). CONCLUSION: Mixed nodular GGOs (MNGGOs) had the potential for growth; most were pathologically adenocarcinoma or BAC. By contrast, PNGGOs were stable for several months to years; most were AAH, BAC, or focal interstitial fibrosis

J Comput Assist Tomogr. 2008 Sep-Oct;32(5):792-8. Performance evaluation of 4 measuring methods of ground-glass opacities for predicting the 5-year relapse-free survival of patients with peripheral nonsmall cell lung cancer: a multicenter study. Kakinuma R, Kodama K, Yamada K, Yokoyama A, Adachi S, Mori K, Fukuyama Y, Kuriyama K, Oda J, Noguchi M, Matsuno Y, Yokose T, Ohmatsu H, Nishiwaki Y. Source National Cancer Hospital East, Kashiwa, Chiba, Japan. rkaki@ncc.go.jp Erratum in J Comput Assist Tomogr. 2009 Jul-Aug;33(4):649. Fukuda, Yasuro [corrected to Fukuyama, Yasuro]; Oda, Junji [corrected to Oda, Junichi]. Abstract OBJECTIVE: To evaluate the performance of 4 methods of measuring the extent of ground-glass opacities as a means of predicting the 5-year relapse-free survival of patients with peripheral nonsmall cell lung cancer (NSLC). METHODS: Ground-glass opacities on thin-section computed tomographic images of 120 peripheral NSLCs were measured at 7 medical institutions by the length, area, modified length, and vanishing ratio (VR) methods. The performance (Az) of each method in predicting the 5- year relapse-free survival was evaluated using receiver operating characteristic analysis. RESULTS: The mean Az value obtained by the length, area, modified length, and VR methods in the receiver operating characteristic analyses was 0.683, 0.702, 0.728, and 0.784, respectively. The differences between the mean Az value obtained by the VR method and by the other 3 methods were significant. CONCLUSIONS: Vanishing ratio method was the most accurate predictor of the 5-year relapse-free survival of patients with peripheral NSLC.

Ann Thorac Surg. 2006 Oct;82(4):1508-10. Multiple lung adenocarcinomas showing ground-glass opacities on thoracic computed tomography. Tsushima Y, Suzuki K, Watanabe S, Kusumoto M, Tsuta K, Matsuno Y, Asamura H. Source Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Chuo-ku, Japan. Abstract It is difficult to distinguish multiple primary lung cancers from pulmonary metastasis. We experienced a case of surgically resected lung tumors that showed multiple ground-glass opacities on thoracic computed tomographic scan. There were eight nonsolid and two part-solid ground-glass opacities in the bilateral lungs. Surgical resection was performed because all tumors had a ground-glass opacity appearance on computed tomographic scan, which is compatible with a finding of primary lung adenocarcinoma. The postoperative pathologic diagnoses were two cases of invasive adenocarcinoma, six cases of bronchioloalveolar carcinoma, and eight cases of atypical adenomatous hyperplasia. The patient remains alive without any evidence of recurrence 40 months after surgery. A ground-glass opacity appearance on computed tomographic scan could be interpreted as supportive evidence for multiple primary lung adenocarcinoma rather than pulmonary metastases.

Chest. 2008 Jun;133(6):1402-9. Pulmonary nodular ground-glass opacities in patients with extrapulmonary cancers: what is their clinical significance and how can we determine whether they are malignant or benign lesions? Park CM, Goo JM, Kim TJ, Lee HJ, Lee KW, Lee CH, Kim YT, Kim KG, Lee HY, Park EA, Im JG. Source Department of Radiology, Seoul National University Hospital, Jongno-Gu, Seoul, South Korea. Abstract BACKGROUND: The clinical significance of pulmonary nodular ground-glass opacities (NGGOs) in patients with extrapulmonary cancers is not known, although there is an urgent need for study on this topic. The purpose of this study, therefore, was to investigate the clinical significance of pulmonary NGGOs in these patients, and to develop a computerized scheme to distinguish malignant from benign NGGOs. METHODS: Fifty-nine pathologically proven pulmonary NGGOs in 34 patients with a history of extrapulmonary cancer were studied. We reviewed the CT scan characteristics of NGGOs and the clinical features of these patients. Artificial neural networks (ANNs) were constructed and tested as a classifier distinguishing malignant from benign NGGOs. The performance of ANNs was evaluated with receiver operating characteristic analysis. RESULTS: Twenty-eight patients (82.4%) were determined to have malignancies. Forty NGGOs (67.8%) were diagnosed as malignancies (adenocarcinomas, 24; bronchioloalveolar carcinomas, 16). Among the rest of the NGGOs, 14 were atypical adenomatous hyperplasias, 4 were focal fibrosis, and 1 was an inflammatory nodule. There were no cases of metastasis appearing as NGGOs. Between malignant and benign NGGOs, there were significant differences in lesion size; the presence of internal solid portion; the size and proportion of the internal solid portion; the lesion margin; and the presence of bubble lucency, air bronchogram, or pleural retraction (p < 0.05). Using these characteristics, ANNs showed excellent accuracy (z value, 0.973) in discriminating malignant from benign NGGOs. CONCLUSIONS: Pulmonary NGGOs in patients with extrapulmonary cancers tend to have high malignancy rates and are very often primary lung cancers. ANNs might be a useful tool in distinguishing malignant from benign NGGOs

Eur Respir J. 2009 Apr;33(4):821-7. doi: 10. 1183/09031936. 00047908 Eur Respir J. 2009 Apr;33(4):821-7. doi: 10.1183/09031936.00047908. Epub 2008 Dec 1. Differential diagnosis and management of focal ground-glass opacities. Infante M, Lutman RF, Imparato S, Di Rocco M, Ceresoli GL, Torri V, Morenghi E, Minuti F, Cavuto S, Bottoni E, Inzirillo F, Cariboni U, Errico V, Incarbone MA, Ferraroli G, Brambilla G, Alloisio M, Ravasi G. Source Dept of Thoracic Surgery, IRCCS Istituto Clinico Humanitas, Milan, Italy. maurizio.infante@humanitas.it Abstract Focal pulmonary ground-glass opacities (GGOs) can be associated with bronchioloalveolar carcinoma. The present retrospective study aimed to test the validity of a multistep approach to discriminate malignant from benign localised (focal) GGOs, identifies useful diagnostic features on computed tomography (CT), and suggests appropriate management guidelines. A stepwise approach, including oral antibiotics, follow-up high-resolution CT (HRCT) 40-60 days later and CT-guided core biopsy, was used. All cases with localised GGOs detected since 2001 were reviewed. CT features were described according to a structured scheme. In total, 40 patients were evaluated. Of these, 11 patients were diagnosed with benign GGOs, 19 patients had lung cancer and 10 were undetermined. Nonpolygonal shape, apparent radial growth and clear-cut margins were associated with a malignant histology. The specificity of CT findings was low. Diagnostic accuracy increased after oral antibiotics, follow-up HRCT and percutaneous core biopsy. Overall, 18 patients underwent surgery for lung cancer. In conclusion, malignant ground-glass opacities have a fairly typical appearance, but some benign lesions closely mimic their malignant counterparts. The stepwise approach adopted in the present study increased the diagnostic specificity and reduced time to definitive diagnosis. Segmentectomy might be the ideal resection volume for such tumours

AJR Am J Roentgenol. 2010 Aug;195(2):W131-8. doi: 10.2214/AJR.09.3828. Multiple focal pure ground-glass opacities on high-resolution CT images: Clinical significance in patients with lung cancer. Tsutsui S, Ashizawa K, Minami K, Tagawa T, Nagayasu T, Hayashi T, Uetani M. Source Nagasaki University Graduate School of Biomedical Sciences, Japan. Abstract OBJECTIVE: The purpose of this study was to evaluate the clinical significance of multiple focal pure ground-glass opacities (GGOs) on high-resolution CT images of patients with lung cancer. MATERIALS AND METHODS: The cases of 23 patients with proven lung cancer and associated multiple focal pure GGOs on high-resolution CT images were retrospectively reviewed. The number, size, distribution, and morphologic characteristics of focal pure GGOs were evaluated. Serial changes in focal pure GGOs that were not surgically resected were analyzed at follow-up high-resolution CT. RESULTS: The number of focal pure GGOs was 196 in total. The size of the opacities ranged from 2 to 30 mm in largest diameter. Lung cancer and focal pure GGOs were seen in the same lobe and/or in the other lobes. One hundred seventy-one of the lesions (87%) had a well- defined border or round shape. Histologic findings were obtained for 15 lesions representing 74 focal pure GGOs that were surgically resected: 11 atypical adenomatous hyperplasia lesions, three bronchioloalveolar carcinomas, and one lesion of focal fibrosis. In 110 of the cases of focal pure GGOs, all of which were followed up with HRCT for a median duration of 1,351 days, the size of 105 lesions (95%) did not change, the size of one decreased, and four lesions disappeared. CONCLUSION: The size of most focal pure GGOs associated with lung cancer did not change during the follow-up period. Most of the small number of lesions histologically diagnosed were atypical adenomatous hyperplasia or bronchioloalveolar carcinoma. These data justify the therapeutic strategy of resecting the primary tumor without therapeutic intervention in the remaining focal pure GGOs

J Radiol. 2009 Nov;90(11 Pt 2):1869-92. [Localized pure or mixed ground-glass lung opacities]. [Article in French] Félix L, Lantuejoul S, Jankowski A, Ferretti G. Source Clinique Universitaire de Radiologie et Imagerie Médicale, Pôle d'Imagerie, CHU de Grenoble, France. lfelix@chu-grenoble.fr Abstract Localized ground-glass opacities (GGOs) have been recently individualized and account for between 2.9% and 19% of all pulmonary nodules detected in high-risk patients included in CT screening series for lung cancer. These opacities, nodular, lobular or flat, correspond to benign lesions (localised infectious and inflammatory diseases, focal interstitial fibrosis, and atypical alveolar hyperplasia) or malignant lesions (bronchioloalveolar carcinoma, early-stage adenocarcinoma and sometimes metastases). Localized GGOs are more likely to be malignant than solid nodules and prognosis is related to the percentage of the ground-glass component. However, doubling time of pure localized malignant GGOs is longer than mixed localized malignant GGOs and even longer than the doubling time of solid malignant nodules. Therefore, localized GGOs warrant a dedicated diagnostic workup.

Am J Respir Crit Care Med. 2012 Feb 15;185(4):363-72.. Decision making in patients with pulmonary nodules. Ost DE, Gould MK. Source Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77002, USA. dost@mdanderson.org Abstract Integrating current evidence with fundamental concepts from decision analysis suggests that management of patients with pulmonary nodules should begin with estimating the pretest probability of cancer from the patient's clinical risk factors and computed tomography characteristics. Then, the consequences of treatment should be considered, by comparing the benefits of surgery if the patient has lung cancer with the potential harm if the patient does not have cancer. This analysis determines the "treatment threshold," which is the point around which the decision centers. This varies widely among patients depending on their cardiopulmonary reserve, comorbidities, and individual preferences. For patients with a very low probability of cancer, careful observation with serial computed tomography is warranted. For those with a high probability of cancer, surgical diagnosis is warranted. For patients in the intermediate range of probabilities, either computed tomography-guided fine-needle aspiration biopsy or positron emission tomography, possibly followed by computed tomography-guided fine-needle aspiration biopsy, is best. Patient preferences should be considered because the absolute difference in outcome between strategies may be small. The optimal approach to the management of patients with pulmonary nodules is evolving as technologies develop. Areas of uncertainty include quantifying the hazard of delayed diagnosis; determining the optimal duration of follow-up for ground-glass and semisolid opacities; establishing the roles of volumetric imaging, advanced bronchoscopic technologies, and limited surgical resections; and calculating the cost-effectiveness of different strategies.

Cancer Imaging. 2013 Sep 23;13(3):365-73. doi: 10. 1102/1470- 7330 Incidental, subsolid pulmonary nodules at CT: etiology and management. Seidelman JL, Myers JL, Quint LE. Source Department of Radiology. Abstract Pulmonary nodules, both solid and subsolid, are common incidental findings on computed tomography (CT) studies. Subsolid nodules (SSNs) may be further classified as either pure ground-glass nodules or part-solid nodules. The differential diagnosis for an SSN is broad, including infection, organizing pneumonia, inflammation, hemorrhage, focal fibrosis, and neoplasm. Adenocarcinomas of the lung are currently the most common type of lung cancer, representing 30-35% of all primary lung tumors, and the subtype of bronchioloalveolar cell carcinoma (BAC) commonly presents as an SSN. In 2011, a new classification system for lung adenocarcinomas was proposed by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society. An important feature of the new system is the relinquishment of the term BAC in favor of more specific histologic subtypes. It has been reported that these subtypes are associated with characteristic CT findings. This article reviews the new classification system of lung adenocarcinomas, discusses and illustrates the associated CT findings, and outlines the current recommendations for further diagnosis, treatment, and follow-up of SSNs based on computed tomography findings.

J Thorac Oncol. 2012 Oct;7(10):1541-6. Long-term surveillance of ground-glass nodules: evidence from the MILD trial. Silva M, Sverzellati N, Manna C, Negrini G, Marchianò A, Zompatori M, Rossi C, Pastorino U. Source Department of Clinical Sciences, Section of Diagnostic Imaging, University of Parma, Italy. Erratum in J Thorac Oncol. 2012 Nov;7(11):e33. Mario, Silva [corrected to Silva, Mario]; Nicola, Sverzellati [corrected to Sverzellati, Nicola]; Carmelinda, Manna [corrected to Manna, Carmelinda]; Giulio, Negrini [corrected to Negrini, Giulio]; Alfonso, Marchianò [corrected to Marchianò, Alfonso]; Maurizio, Zompatori [corrected to Zompatori, Maurizio]; Cristina, Rossi [corrected to Rossi, Cristina]; Ugo, Pastorino [corrected to Pastorino, Ugo]. Abstract INTRODUCTION: The purpose of this study was to evaluate the natural evolution of ground-glass nodules (GGNs) in the Multicentric Italian Lung Detection (MILD) trial, which adopted a nonsurgical approach to this subset of lesions. METHODS: From September 2005 to August 2007, 56 consecutive MILD participants with 76 GGNs were identified from 1866 individuals who underwent baseline low-dose computed tomography. The features of GGNs were assessed and compared with the corresponding repeat low-dose computed tomographies after a mean time of 50.26 ± 7.3 months. The GGNs were classified as pure (pGGN) or part-solid (psGGN) GGNs. The average of the maximum and the minimum diameters for both pGGNs and psGGNs and the maximum diameter of the solid portion of psGGNs were manually measured. At follow-up, GGNs were classified as follows: resolved, decreased, stable, or progressed (according to three defined growth patterns). RESULTS: A total of 15 of 48 pGGNs (31.3%) resolved, 4 of 48 (8.3%) decreased in size, 21 of 48 (43.8%) remained stable, and 8 of 48 (16.7%) progressed. Among the psGGNs with a solid component smaller than 5 mm, 3 of 26 (11.5%) resolved, 11 of 26 (42.3%) remained stable, and 12 of 26 (46.2%) progressed. One of the two psGGNs with a solid component larger than 5 mm remained stable, and the other decreased in size. Four lung cancers were detected among the GGN subjects, but only one arose from a psGGN, and was resected in stage Ia. CONCLUSIONS: The progression rate of the GGNs toward clinically relevant disease was extremely low in the MILD trial and supports an active surveillance attitude.