Abstract
Background
This study aimed to investigate the radiological, pathological, and prognostic characteristics of large consolidative‐type pulmonary invasive mucinous adenocarcinomas (IMA).
Methods
We retrospectively reviewed 738 patients who confirmed IMA between January 2010 and August 2022, and two radiologists reviewed imaging data to determine subtypes. We included 41 patients with pathologically large consolidative‐type IMA. We analyzed their radiological, pathological, and prognostic characteristics. The recurrence‐free survival (RFS) and overall survival (OS) were determined using the Kaplan–Meier method.
Results
Most lesions were located in the lower lobe, with 46.3% patients showing multiple lesions. Halo, angiogram, vacuole, air bronchogram, and dead branch sign were observed in 97.6%, 73.2%, 63.4%, 61.0%, and 61.0% of the cases, respectively. Unevenly low enhancement was observed in 88.89% of patients. T3 and T4 pathological stages were observed in 50.0% and 30.6% of patients, respectively. Lymph node metastasis was observed in 16.7% patients, with no distant metastasis. Spread‐through air spaces and intrapulmonary dissemination were observed in 27.8% and 19.4% patients, respectively. Moreover, Kirsten rat sarcoma viral oncogene mutations were found in 68.6% of cases, and no epidermal growth factor receptor mutations were seen. Among all mutation sites, G12V mutation is the most common, accounting for 40%. The average RFS and OS were 19.4 and 66.4 months, respectively, with 3‐year RFS and OS rates of 30.0% and 75.0%, respectively. Pleural invasion and lymph node metastasis were independent risk factors for diagnosis.
Conclusion
Halo, vacuole, angiogram, and dead branch signs were frequently observed in consolidative‐type IMA. Kirsten rat sarcoma viral oncogene mutations are common in consolidative‐type IMA, especially site G12V, whereas epidermal growth factor receptor mutations were rare; therefore, gene immunotherapy was more difficult. Most patients were in stage T3–T4; however, lymph node metastasis was rare.
Keywords: computed tomography, mucinous adenocarcinoma, pathology, prognosis, radiology
Invasive mucinous adenocarcinoma (IMA) accounts for approximately 2%–10%, and large consolidative‐type IMA has a low clinical incidence, which has diverse radiological manifestations, with halo, vacuole, angiogram, and dead branch signs being frequently observed. The T stage of large consolidative‐type IMA is relatively late, and lymph node metastasis is rare. KRAS mutations were common in consolidative‐type IMA, whereas EGFR mutations were rare. Consolidative‐type IMA has a poor prognosis.
1. INTRODUCTION
Worldwide, lung cancer has the highest mortality rate and the second‐highest incidence rate after breast cancer. 1 Adenocarcinoma is the most common pathological pattern. Invasive adenocarcinomas can be classified as mucinous adenocarcinoma (IMA) and non‐mucinous adenocarcinoma. 2 IMA was once known as mucinous bronchioloalveolar carcinoma. In 2011, the International Association for Lung Cancer Research/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma completely discontinued the use of “bronchioloalveolar carcinoma” and proposed using “IMA.” 3 The 5th edition of the World Health Organization classification of tumors continued this use. 4 IMA accounts for approximately 2%–10% of lung adenocarcinomas. 5 Pathologically, IMA tumor cells show goblet and/or columnar morphology with abundant intracytoplasmic mucin and small, basally oriented nuclei. Nuclear atypia is usually inconspicuous or absent. The surrounding alveolar spaces are often mucin‐filled. 4 Based on the percentage of mucinous type cells, IMA can be classified as a pure mucinous type (invasive mucinous type > 90%) or mixed mucinous/non‐mucinous type (non‐mucinous invasive component ≥ 10%). 6 Radiologically, IMA has diverse imaging manifestations, including low density, vacuoles, halos, air bronchograms, and spiculation. 7 , 8 Using computed tomography (CT) data, IMA can be divided into the nodular/mass and consolidative/pneumonic types, with the former being common and the latter being rare. The consolidative/pneumonic type is often misdiagnosed as an inflammatory disease, leading to delayed treatment and worsening prognosis. However, few studies have focused on the consolidative/pneumonic type of IMA. Accordingly, this study aimed to investigate the radiological, pathological, and prognostic characteristics of large consolidative‐type pulmonary IMA. This could improve diagnosis, treatment, and follow‐up for patients with consolidative‐type IMA.
2. MATERIALS AND METHODS
This retrospective study was approved by the ethics committee of our institution, which waived the requirement for informed consent.
2.1. Patients
We retrospectively reviewed patients with pathologically confirmed IMA between January 2010 and August 2022. The inclusion criteria were as follows: (1) IMA diagnosed through surgery or puncture biopsy and (2) large consolidative‐type features on chest thin‐slice CT within 1 month prior to surgery. The exclusion criteria were as follows: (1) chest thin‐slice CT showing the IMA as a nodular/mass or patch type; (2) pathological findings not accurately matching the chest CT findings; (3) poor CT image quality; and (4) missing clinical, radiological, or pathological data (Figure 1). We collected 738 cases of IMA, and after reviewing imaging data, finally, 41 cases of large consolidative‐style IMA pathologically and radiologically were included in the study. In this study, patients received neoadjuvant chemotherapy or postoperative chemotherapy, using cisplatin/carboplatin + pemetrexed/paclitaxel as the medication. Only one patient with bone metastasis received four courses of radiation therapy without undergoing chemotherapy.
FIGURE 1.
Flowchart of the study population. Numbers in parentheses are the numbers of patients.
2.2. CT scanning protocol
A 64‐row spiral CT scanner (LightSpeed VCT, Discovery CT750 HD, or Optima CT66; GE HealthCare, Chicago, IL, USA) was used. The CT parameters were as follows: tube voltage, 120 kVp; auto mA settings, tube current, approximately 200–350 mA; noise index, 13; pitch, 0.992 or 0.984; rotation time, 0.5 s; thickness, 5 mm; lung window width of 1600 Hounsfield units (HU) and level of −600 HU; and mediastinal window width of 360 HU and level of 60 HU. The reconstruction thicknesses were 1.25 or 1.0 mm; moreover, the intervals were 0.8 mm using a standard reconstruction algorithm. For enhanced CT scans, iopromide (iodine concentration, 300 mg/mL) was injected at a dose of 80–90 mL and a flow rate of 2.5 mL/s and used as the contrast agent. Subsequently, images were obtained 35 s after contrast agent injection.
2.3. Analyses of clinical and radiological characteristics
The clinical and radiological characteristics of the included patients were reviewed. The clinical characteristics included age, sex, symptoms, smoking history, malignancy history, diagnosis method, and operation duration. CT features included the lesion type (nodular/mass/patch/large consolidative type) (Figure 2), location, number (single or multiple), volume proportion of lung lobes occupied, and morphological features (including halo sign, dead branch sign, angiogram sign, vacuole sign, and cavity sign; Figure 3). The definition criteria for large consolidative‐type IMA were (1) the lesion occupied at least one lung lobe; (2) the main lesion volume accounted for 1/5th or more of the lung lobe volume; or (3) the main lesion crossed the inner, middle, and outer zones of the lung lobe (Figure 4). The aforementioned CT characteristics were analyzed on multiplanar reconstruction images by two radiologists with 2 and 7 years of experience in chest CT. Disagreements were resolved through consultation with a senior radiologist with 25 years of experience in chest CT.
FIGURE 2.
The CT imaging classification of invasive mucous adenocarcinoma (IMA). (A) CT imaging of nodular‐type IMA (d < 3 cm), (B) mass‐type IMA (d ≥ 3 cm), (C) patch‐type IMA, and (D) large consolidative‐type IMA.
FIGURE 3.
The CT features of large consolidative‐type invasive mucinous adenocarcinoma (IMA). (A) Halo sign refers to the ground glass shadow around the lesion, which results from the infiltration of a large amount of mucus and macrophages around the lesion area. (B) Angiogram sign refers to obvious enhancement of vascular shadow passes through the low‐density consolidation image on the enhanced CT. (C) Air bronchus and dead branch sign mean that the bronchus shadow can be seen in the consolidation area. The smooth bronchus is called the “air bronchus,” and the twisted and invaded bronchus is called “dead branch sign.” (D) Vacuole sign refers to the gas‐containing part of the lung with a diameter usually <5 mm. A cavity is produced by the expulsion or drainage of a necrotic part of the lesion via the bronchial tree with a diameter usually >5 mm.
FIGURE 4.
The large consolidative‐type invasive mucinous adenocarcinoma (IMA) was defined as follows: (A) the lesion occupied at least one lung lobe; (B) the main lesion volume accounted for 1/5 or more of the lung lobe volume; or (C) the main lesion crossed the inner, middle, and outer zones of the lung lobe.
2.4. Pathological analysis
A senior pathologist with 20 years of experience reviewed histopathology slides of samples from all eligible patients based on the 2021 World Health Organization classification of lung adenocarcinomas and the 8th edition TNM staging of lung cancer. In this study, professional pathologists used elastic fiber staining to determine whether there was pleural invasion. Continuous pleural elastic fibers could be seen by staining with pleural elastic fibers (without pleural invasion). When pleural invasion occurs, it manifests as discontinuous elastic fibers. Moreover, molecular analyses of mutations of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) were performed using a polymerase chain reaction‐based amplification refractory mutation system with the Human EGFR Gene Mutations Detection Kit (Beijing ACCB Biotech Ltd., Beijing, China).
2.5. Follow‐up
Postoperative follow‐up data were obtained from medical records or telephone interviews. The follow‐up endpoint was May 30, 2022. Recurrence‐free survival (RFS) was defined as the period from the operation date to the date of recurrence or death from any cause or the follow‐up endpoint. Recurrence referred to recurrence adjacent to the surgical area, pulmonary recurrence, mediastinal recurrence, or distant recurrence. Overall survival (OS) was defined from the operation date to the date of death from any cause. We calculated the 3‐year RFS and OS rates for patients who were followed up for ≥3 years.
2.6. Statistical analyses
All statistical analyses were performed using SPSS software (v23.0; IBM Corp., Armonk, NY, USA). Normally and non‐normally distributed continuous variables are expressed as mean ± standard deviation and median (range), respectively. Categorical data are presented as numbers (percentages). The Kaplan–Meier method was used to calculate the cumulative survival rate and plot survival curves. Univariate analyses were used to identify prognostic factors for IMA using Kaplan–Meier analysis with the log‐rank test. To determine independent predictors of IMA prognosis, we performed multivariate Cox proportional hazards regression with forward stepwise selection, with adjustment for variables with P‐values of <0.20 in the univariate analyses. Statistical significance was set at P < 0.05.
3. RESULTS
3.1. Clinical features
Among the 41 included patients, there were 22 women and 19 men (mean age: 61.00 ± 9.31 years [range: 37–78 years]). Only one patient had a history of malignancy (lung adenocarcinoma); further, 13 patients had a smoking history. There were clinical symptoms in 24 (58.54%) patients, including cough (n = 24), sputum (n = 14), and hemoptysis (n = 7). Finally, diagnosis was confirmed in 36 and five patients by surgical pathology and CT‐guided aspiration biopsy, respectively (Table 1).
TABLE 1.
Clinical and radiological characteristics of large consolidative‐type IMA.
| Clinical features | |
|---|---|
| Age (years) | 61.00 ± 9.31 |
| Gender | |
| Male | 19 (46.34%) |
| Female | 22 (53.66%) |
| Smoking history | 13 (31.71%) |
| Symptom | |
| Coughing | 24 (58.54%) |
| Sputum | 14 |
| Hemoptysis | 7 |
| History of Malignancy | 1 |
| Diagnosis method | |
| Surgery | 36 |
| Puncture biopsy | 5 |
| Radiological features | |
| Location | |
| Right | |
| Upper | 3 |
| Middle | 4 |
| Lower | 14 |
| Left | |
| Upper | 4 |
| Lower | 20 |
| Both lungs | 1 |
| Number of lesions | |
| Single lesion | 22 (53.66%) |
| Multiple lesions | 19 (46.34%) |
| Proportion of lung lobe occupied | |
| Unilateral lung | 38 |
| Single lobe | 35 |
| 1/5 | 1 |
| 1/4 | 4 |
| 1/3 | 9 |
| 1/2 | 11 |
| 2/3 | 6 |
| 1 | 4 |
| Multiple lobes | 3 |
| Bilateral lung | 3 |
| Average diameter (cm) | 8.90 ± 2.59 |
| Morphological characteristics | |
| Pleural retraction | 40 (97.56%) |
| Halo sign | 40 (97.56%) |
| Angiogram sign | 30 (73.17%) |
| Vacuole sign | 26 (63.41%) |
| Dead branch sign | 25 (60.98%) |
| Air bronchogram sign | 25 (60.98%) |
| Cavities | 9 (21.95%) |
| Necrosis | 5 (12.20%) |
| Calcification | 2 (4.88%) |
| Pleural effusion | 1 (2.44%) |
| Enhancement patterns | |
| Low enhancement | 3 (8.33%) |
| Uneven low enhancement | 32 (88.89%) |
| Significant enhancement | 1 (2.78%) |
Note: Values are expressed as number (%), mean ± standard deviation, or median (range).
3.2. Radiological features
Table 1 presents the radiological characteristics of the patients with large consolidative‐type IMA. The lesions were mostly located in the bilateral lower lung lobes (35/41, 85.37%). CT imaging revealed single and multiple lesions in 22 (53.66%) and 19 (46.34%) patients, respectively. Additionally, 38 patients showed involvement of unilateral lung fields (including 35 and three patients with involvement of one and two lung lobes, respectively), and three patients showed involvement of bilateral lung fields. Among the 35 cases involving a single lung lobe, 1, 4, 9, 11, 6, and 4 cases showed involvement of 1/5th, 1/4th, 1/3rd, 1/2, 2/3, and a full lung lobe, respectively. Among the three cases involving bilateral lungs, two and one involved two and five lobes, respectively. The mean diameter of the main lesions was 8.90 ± 2.59 cm. Regarding the morphological features, halo, angiogram, vacuole, air bronchogram, and dead branch sign were observed in 40 (97.56%), 30 (73.17%), 26 (63.41%), 25 (60.98%), and 25 cases (60.98%), respectively; moreover, cavities and necrosis were observed in nine (21.95%) and five (12.20%) cases. Only two (4.88%) and one (2.44%) case had calcification and pleural effusion, respectively.
3.3. Pathological features and genetic testing
IMAs contained basal, ciliated columnar epithelial, and mucus cells. Surgical resection was performed on 36 patients; among them, 7, 18, and 11 cases were in the T2, T3, and T4 stages, respectively. Further, 16.67% (6/36) of these patients presented lymph node metastasis (N1 stage, n = 4; N2 stage, n = 2), whereas 83.33% (30/36) had no lymph node metastasis. There were no cases of distant metastases. Pleural invasion, spread‐through air spaces (STAS), and intrapulmonary dissemination were observed in 33.33% (5/15, 21 not tested), 27.78% (10/36), and 19.44% (7/36) of the patients, respectively. In this study, 21 cases did not undergo elastic fiber staining. Additionally, 35 patients underwent genetic testing; among them, 24 (68.57%), 1 (2.86%), and 0 (0%) showed KRAS, vrafmurine sarcoma viral oncegene homolog B (BRAF), and EGFR mutations, respectively (Table 2). Further analysis of the gene mutation sites showed six KRAS mutation sites; among them, 1 (4%), 3 (12%), 8 (32%), 1 (4%), 10 (40%), and 1 (4%) showed G12A, G12C, G12D, G12S, G12V, and G13D mutation sites, respectively (Figure 5).
TABLE 2.
Pathological characteristics and genetic testing of large consolidative‐type IMA.
| Pathological features and genetic testing | |
|---|---|
| Intrapulmonary dissemination | |
| Yes | 7 (19.44%) |
| No | 29 (80.56%) |
| Pleural invasion | |
| Yes | 5 (33.33%) |
| No | 10 (66.67%) |
| Not tested | 21 |
| STAS | 10 (27.78%) |
| Pathological maximum diameter (cm) | 8.81 ± 2.40 |
| Pathological staging | |
| T | |
| 2 | 7 (19.44%) |
| 3 | 18 (50.00%) |
| 4 | 11 (30.56%) |
| N | |
| 0 | 30 (83.33%) |
| 1 | 4 (11.11%) |
| 2 | 2 (5.56%) |
| M | |
| 0 | 36 (100%) |
| Genetic testing | |
| EGFR mutation | 0 (0%) |
| KRAS mutation | 24 (68.57%) |
Note: Values are expressed as number (%), mean ± standard deviation, or median (range).
Abbreviations: BRAF, vrafmurine sarcoma viral oncegene homolog B; EGFR, epidermal growth factor receptor; KRAS, Kirsten rat sarcoma viral oncogene; STAS, spread through air spaces.
FIGURE 5.
Pie chart of the gene mutation points in this study. The percentage on the chart is the percentage of patients with mutations at this site.
3.4. Prognostic analysis
Among the 36 patients who underwent surgical resection, five were lost to follow‐up. The median follow‐up duration of the remaining 31 patients was 35.5 months (6.5–95.6 months). During follow‐up, 19 cases showed progression, including 15, 1, 1, 1, and 1 case of intrapulmonary, liver, brain, bone, and peritoneal metastasis, respectively. Moreover, eight patients died during follow‐up. The median RFS and mean OS of the included patients were 19.37 months (1.13, 86.80) and 66.42 ± 5.75 months, respectively. Twenty patients were followed up for ≥3 years. The 3‐year RFS and OS rates were 30.0% and 75.0%, respectively (Table 3).
TABLE 3.
Prognosis of large consolidative‐type IMA.
| Prognosis | |
|---|---|
| Progress | |
| No | 12 (34.48%) |
| Yes | 19 (65.52%) |
| Lung | 15 |
| Brain | 1 |
| Liver | 1 |
| Bone | 1 |
| Peritoneum | 1 |
| Death | |
| No | 23 (74.19%) |
| Yes | 8 (25.81%) |
| RFS (months) | 19.37 (1.13,86.80) |
| 3 years RFS (%) | 30.00% |
| OS (months) | 66.42 ± 5.75 |
| 3 years OS (%) | 75.00% |
Note: Values are expressed as number (%), mean ± standard deviation, or median (range).
Abbreviations: OS, overall survival; RFS, relapse‐free survival.
Follow‐up patients will be divided into low‐risk and high‐risk groups based on their progression, with the low‐risk group indicating no progression (n = 12) and the high‐risk group indicating progression (n = 19). We performed univariate and multivariate analyses on patients followed up (n = 31) to identify prognostic factors for IMA (Table 4). Multivariate analysis revealed that pleural invasion (p = 0.002) and lymph node metastasis (p = 0.019) were independent risk factors for diagnosis of large consolidated‐type IMA (Table 4).
TABLE 4.
Univariate and multivariate analyses of the prognosis of large consolidative‐type IMA.
| Low‐risk group (no progress, N = 12) | High‐risk group (Progress, N = 19) | P‐value | Univariate analysis | Multivariate analysis | |||
|---|---|---|---|---|---|---|---|
| P‐value | P‐value | Exp(B) | 95% CI | ||||
| Gender | 0.756 | 0.915 | |||||
| Female | 7 | 10 | |||||
| Male | 5 | 9 | |||||
| Age | 62.08 ± 10.79 | 59.11 ± 7.65 | 0.236 | 0.003 | |||
| Smoking history | 2 | 7 | 0.418 | 0.434 | |||
| Symptoms | 5 | 13 | 0.141 | 0.328 | |||
| Percentage of lung lobes | 1/3 (1/4,2/3) | 1/2 (1/5,2) | 0.12 | 0.219 | |||
| Air bronchogram sign | 6 | 12 | 0.47 | 0.500 | |||
| Vacuole sign | 9 | 13 | 0.694 | 0.777 | |||
| Cavities | 2 | 7 | 0.418 | 0.351 | |||
| Necrotic | 2 | 2 | 0.619 | 0.586 | |||
| Pleural retraction | 12 | 18 | 0.419 | 0.955 | |||
| Halo sign | 12 | 19 | |||||
| Angiogram sign | 8 | 15 | 0.447 | 0.749 | |||
| Dead branch sign | 6 | 12 | 0.470 | 0.701 | |||
| Multifocal | 7 | 7 | 0.242 | 0.891 | |||
| Calcification | 1 | 1 | 0.735 | 0.260 | |||
| Average diameter | 8.033 ± 1.281 | 9.097 ± 2.538 | 0.022 | 0.000 | |||
| Pathological max diameter | 8.200 ± 1.842 | 9. 116 ± 2.845 | 0.046 | 0.034 | |||
| Intrapulmonary dissemination | 2 | 3 | 0.948 | 0.647 | |||
| Pleural invasion | 0 | 4 | 0.221 | 0.004 | 0.002 | 0.108 | 0.027, 0.434 |
| T Staging | 0.112 | 0.127 | |||||
| T2 | 1 | 6 | |||||
| T3 | 9 | 7 | |||||
| T4 | 2 | 6 | |||||
| Lymph node metastasis | 1 | 4 | 0.624 | 0.068 | 0.019 | 0.224 | 0.064, 0.780 |
| STAS | 2 | 6 | 0.433 | 0.149 | |||
| KRAS mutation | 8 | 13 | 0.831 | 0.389 | |||
Note: Values are expressed as number (%), mean ± standard deviation, or median (range).
Abbreviations: KRAS, Kirsten rat sarcoma viral oncogene; STAS, spread through air spaces.
4. DISCUSSION
We investigated the clinical, radiological, and pathological characteristics of large consolidative‐type IMA. Large consolidative‐type IMA has a low clinical incidence. We found that IMA was most common in the elderly population. Further, we observed diverse radiological manifestations, including halo, vacuole, angiographic, and dead branch sign as well as multifocality. KRAS and EGFR mutations were common and rare, respectively, in consolidative‐type IMA. Upon initial diagnosis of IMA, the pathological stage was usually T3–T4; contrastingly, lymph node metastasis and distant metastasis were rare. Taken together, consolidative‐type IMA has a poor prognosis.
In our study, IMA was mostly located in the lower lobe (35/41, 85.37%), which could be attributed to gravity. IMA has diverse radiological manifestations, with halo, angiographic, and dead branch sign frequently observed and cavities rarely occurring, consistent with previous studies. 8 , 9 , 10 , 11 , 12 However, recent studies have demonstrated that these CT features lack specificity and can be observed in lymphoma or pneumonia, which impedes differentiation of IMA. IMA and pneumonia are differentiated mainly based on clinical symptoms and detailed CT features. Compared with IMA, pneumonia involves a shorter disease course and often presents fever symptoms. Further, on CT imaging, lobar pneumonia shows consolidative shadows without bronchial involvement, in which an air bronchogram sign can be observed; contrastingly, IMA shows a dead branch sign. Compared with IMA, pneumonia often involves a significantly larger consolidation area, 13 and lung lymphoma mainly grows along the vascular and bronchial bundles, with frequent dilation of the bronchi and rare occurrences of a bronchial air sign. 14
Pathologically, the IMA originates from the goblet and columnar epithelial cells of the alveolar wall. 15 These cells undergo cancerization and produce a large mucus amount to form a mucus lake, leading to alveolar cavity expansion. 16 Tumor cells that survive with mucus pass through the alveolar wall and spread to other lung regions along the airway, which may lead to the formation of a large consolidative IMA. 17 No clear studies have shown that nodular‐type IMA may be the early stage of large consolidative‐type IM, and our own has not observed cases of nodules developing into large consolidation. This suggests that large consolidative‐type IMA may be an independent IMA subtype.
We found that 19.44% of cases had intrapulmonary dissemination. The dissemination mechanisms of lung cancer include hematogenous dissemination, lymphatic metastasis, direct invasion, and STAS. 16 STAS has a relatively high incidence among IMA cases, which accounted for 27.78% of our cases. In our study, 46.34% of the IMA cases showed multiple lesions, which could be attributed to the spread of tumor cells to other lung tissues along the small airways. 12 , 17 Other studies have demonstrated that mucin (MUC5AC) is crucially involved in the formation of multifocal IMA, 18 which requires further research.
We found that KRAS mutations were common in consolidative‐type IMA (68.57%), of which G12V mutation was the most common, accounting for 40%; however, consistent with previous findings, none of the cases showed EGFR mutations. 18 , 19 Therefore, targeted drugs for KRAS, but not EGFR, mutations are eligible for patients with IMA.
In our study, 80.56% of the patients were initially diagnosed in the T3 and T4 stages, and only 16.67% of the patients were found with lymph node metastasis. This indicates that large consolidative IMAs do not tend to lymph node metastasis, which is consistent with the previous research results. 20 , 21 Because of the clinical insidious nature of the consolidative‐type IMA, the lesions were found to be large and the clinical stage was late initially, so prognosis was affected.
IMA has a better prognosis than non‐mucinous adenocarcinoma. 22 Among IMA cases, the nodular type has a better prognosis than the pneumonic type. 23 NIE et al. 24 reported that the 5‐year RFS rates were 64.7% and 0% for the nodular and pneumonic‐type groups, respectively. Moreover, the pneumonic/consolidative type was an independent risk factor for prognosis. 25 We found a poor prognosis of consolidative‐type IMA, with 3‐year RFS and OS rates of 30.0% and 75%, respectively. Watanabe et al. 18 reported that the 5‐year OS and RFS rates of pneumonic‐type IMA were 20.0% and 0%, respectively. The inconsistency between our findings and those of Watanabe et al. 18 could be attributed to differences in the definitions of consolidative‐type IMA, the pathological stages of the enrolled patients, and inevitable inclusion bias.
Because of the low incidence rate of IMA, and the lower incidence rate of large consolidative type on imaging, the sample size of this study is quite small. However, the sample size of this study is still higher than that of other studies in recent years, for example, Wang et al. 8 recorded 26 cases of pneumonia‐type IMA; Huo et al. 10 only recorded 21 cases of pneumonia‐type IMA; and Han et al. 17 recorded 17 cases of pneumonia‐type lung cancer.
This study has several limitations. First, this was a single‐center retrospective study, which may involve inclusion bias and heterogeneous CT scan protocols. Second, we included a relatively small number of cases. Finally, some of the patients were lost to follow‐up. In conclusion, large consolidative‐type IMA tends to occur in the elderly population. It has diverse radiological manifestations, with frequent presentation of halo, angiographic, and dead branch sign. KRAS mutations are common, whereas EGFR mutations are rare. Patients initially diagnosed with large consolidative‐type IMA are usually in the T3–T4 stages; however, lymph node metastasis is rare. Finally, consolidative‐type IMA has a poor prognosis.
AUTHOR CONTRIBUTIONS
Conceptualization: Jiaqi Chen, Linlin Qi, Jianwei Wang. Methodology: Jiaqi Chen, Linlin Qi, Jianwei Wang. Methodology validation: Jiaqi Chen, Linlin Qi, Jianwei Wang, Jianwei Wang. Investigation: Qi Xue, Jia Jia, Guochao Zhang. Data curation: Jiaqi Chen, Linlin Qi, Jia Jia, Guochao Zhang. Formal analysis: Jianing Liu, Fenglan Li, Shulei Cui. Writing—original draft: Jiaqi Chen, Linlin Qi. Writing—review and editing: Jiaqi Chen, Linlin Qi, Jianwei Wang. Visualization: Jiaqi Chen, Linlin Qi, Jianwei Wang, Jianwei Wang. Supervision: Jianwei Wang, Jianwei Wang, Qi Xue, Jia Jia, Guochao Zhang, Jianing Liu, Fenglan Li, Shulei Cui. Funding acquisition: Jianwei Wang. All authors contributed to the article and approved the submitted version.
CONFLICT OF INTEREST STATEMENT
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
ETHICS STATEMENT
This retrospective study was approved by the ethics committee of our institution, which waived the requirement for informed consent.
ACKNOWLEDGEMENTS
None.
Chen J, Qi L, Wang J, et al. Radiological and clinical features of large consolidative‐type pulmonary invasive mucinous adenocarcinoma. Clin Respir J. 2024;18(3):18(3):e13743. doi: 10.1111/crj.13743
Jiaqi Chen and Linlin Qi contributed equally to this work as co‐first authors.
Funding information This study has received funding from the National Natural Science Foundation of China (grant 81971616), Beijing Natural Science Foundation (grant 7222148), CAMS Innovation Fund for Medical Sciences (CIFMS) (grant 2021‐I2M‐C&T‐B‐065), and the Special Research Fund for Central Universities, Peking Union Medical College (grant 3332022025).
Contributor Information
Jianwei Wang, Email: dr_jianweiwang@163.com.
Liyan Xue, Email: xuely@cicams.ac.cn.
DATA AVAILABILITY STATEMENT
Research data are not shared. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
REFERENCES
- 1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209‐249. doi: 10.3322/caac.21660 [DOI] [PubMed] [Google Scholar]
- 2. Nicholson AG, Tsao MS, Beasley MB, et al. The 2021 WHO classification of lung tumors: impact of advances since 2015. J Thorac Oncol. 2022;17(3):362‐387. doi: 10.1016/j.jtho.2021.11.003 [DOI] [PubMed] [Google Scholar]
- 3. Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6(2):244‐285. doi: 10.1097/JTO.0b013e318206a221 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. WHO classification of tumours. Thoracic tumours. 5th ed. IARC Press; 2021. [Google Scholar]
- 5. Xu L, Li C, Lu H. Invasive mucinous adenocarcinoma of the lung. Transl Cancer Res. 2019;8(8):2924‐2932. doi: 10.21037/tcr.2019.11.02 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Travis WD, Brambilla E, Noguchi M, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society: international multidisciplinary classification of lung adenocarcinoma: executive summary. Proc am Thorac Soc. 2011;8(5):381‐385. doi: 10.1513/pats.201107-042ST [DOI] [PubMed] [Google Scholar]
- 7. Miyamoto A, Kurosaki A, Fujii T, Kishi K, Homma S. HRCT features of surgically resected invasive mucinous adenocarcinoma associated with interstitial pneumonia. Respirology. 2017;22(4):735‐743. doi: 10.1111/resp.12947 [DOI] [PubMed] [Google Scholar]
- 8. Wang T, Yang Y, Liu X, et al. Primary invasive mucinous adenocarcinoma of the lung: prognostic value of CT imaging features combined with clinical factors. Korean J Radiol. 2021;22(4):652‐662. doi: 10.3348/kjr.2020.0454 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Sawada E, Nambu A, Motosugi U, et al. Localized mucinous bronchioloalveolar carcinoma of the lung: thin‐section computed tomography and fluorodeoxyglucose positron emission tomography findings. Jpn J Radiol. 2010;28(4):251‐258. doi: 10.1007/s11604-009-0414-4 [DOI] [PubMed] [Google Scholar]
- 10. Huo JW, Huang XT, Li X, Gong JW, Luo TY, Li Q. Pneumonic‐type lung adenocarcinoma with different ranges exhibiting different clinical, imaging, and pathological characteristics. Insights Imaging. 2021;12(1):169. doi: 10.1186/s13244-021-01114-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Kim TH, Kim SJ, Ryu YH, et al. Differential CT features of infectious pneumonia versus bronchioloalveolar carcinoma (BAC) mimicking pneumonia. Eur Radiol. 2006;16(8):1763‐1768. doi: 10.1007/s00330-005-0101-5 [DOI] [PubMed] [Google Scholar]
- 12. Yu X, Zhang S, Xu J, et al. Nomogram using CT Radiomics features for differentiation of pneumonia‐type invasive mucinous adenocarcinoma and pneumonia: multicenter development and external validation study. AJR am J Roentgenol. 2023;220(2):224‐234. doi: 10.2214/AJR.22.28139 [DOI] [PubMed] [Google Scholar]
- 13. Jung JI, Kim H, Park SH, et al. CT differentiation of pneumonic‐type bronchioloalveolar cell carcinoma and infectious pneumonia. Br J Radiol. 2001;74(882):490‐494. doi: 10.1259/bjr.74.882.740490 [DOI] [PubMed] [Google Scholar]
- 14. Deng W, Wan Y, Yu JQ. Pulmonary MALT lymphoma has variable features on CT. Sci Rep. 2019;9(1):8657. doi: 10.1038/s41598-019-45144-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Cha YJ, Shim HS. Biology of invasive mucinous adenocarcinoma of the lung. Transl Lung Cancer Res. 2017;6(5):508‐512. doi: 10.21037/tlcr.2017.06.10 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Gaikwad A, Souza CA, Inacio JR, et al. Aerogenous metastases: a potential game changer in the diagnosis and management of primary lung adenocarcinoma. AJR am J Roentgenol. 2014;203(6):W570‐W582. doi: 10.2214/AJR.13.12088 [DOI] [PubMed] [Google Scholar]
- 17. Han J, Wu C, Wu Y, et al. Comparative study of imaging and pathological evaluation of pneumonic mucinous adenocarcinoma. Oncol Lett. 2020;21(2):125. doi: 10.3892/ol.2020.12386 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Watanabe H, Saito H, Yokose T, et al. Relation between thin‐section computed tomography and clinical findings of mucinous adenocarcinoma. Ann Thorac Surg. 2015;99(3):975‐981. doi: 10.1016/j.athoracsur.2014.10.065 [DOI] [PubMed] [Google Scholar]
- 19. Boland JM, Maleszewski JJ, Wampfler JA, et al. Pulmonary invasive mucinous adenocarcinoma and mixed invasive mucinous/nonmucinous adenocarcinoma‐a clinicopathological and molecular genetic study with survival analysis. Hum Pathol. 2018;71:8‐719. doi: 10.1016/j.humpath.2017.08.002 [DOI] [PubMed] [Google Scholar]
- 20. Lee HY, Cha MJ, Lee KS, et al. Prognosis in resected invasive mucinous adenocarcinomas of the lung: related factors and comparison with resected nonmucinous adenocarcinomas. J Thorac Oncol. 2016;11(7):1064‐1073. doi: 10.1016/j.jtho.2016.03.011 [DOI] [PubMed] [Google Scholar]
- 21. Kakegawa S, Shimizu K, Sugano M, et al. Clinicopathological features of lung adenocarcinoma with KRAS mutations. Cancer. 2011;117(18):4257‐4266. doi: 10.1002/cncr.26010 [DOI] [PubMed] [Google Scholar]
- 22. Dermawan JK, Farver CF. The prognostic significance of the 8th edition TNM staging of pulmonary carcinoid tumors: a single institution study with long‐term follow‐up. Am J Surg Pathol. 2019;43(9):1291‐1296. doi: 10.1097/PAS.0000000000001268 [DOI] [PubMed] [Google Scholar]
- 23. Xu X, Shen W, Wang D, et al. Clinical features and prognosis of resectable pulmonary primary invasive mucinous adenocarcinoma. Transl Lung Cancer Res. 2022;11(3):420‐431. doi: 10.21037/tlcr-22-190 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Nie K, Nie W, Zhang YX, Yu H. Comparing clinicopathological features and prognosis of primary pulmonary invasive mucinous adenocarcinoma based on computed tomography findings. Cancer Imaging. 2019;19(1):47. doi: 10.1186/s40644-019-0236-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Yoon HJ, Kang J, Lee HY, et al. Recurrence dynamics after curative surgery in patients with invasive mucinous adenocarcinoma of the lung. Insights Imaging. 2022;13(1):64. doi: 10.1186/s13244-022-01208-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Research data are not shared. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.