What Is Bronchioloalveolar Carcinoma?

Under light microscopy, pure bronchioloalveolar carcinoma can be divided into mucinous (20% to 25%), non-mucinous (60% to 65%), and mixed (12% to 14%). According to the general morphology and imaging manifestations of the lesions, it can be divided into three types: (1) Solitary pulmonary nodules: a single lesion, mostly located under the visceral pleura around the lung tissue, round or lobular, and the cut surface is gray , Usually without bleeding and tumor necrosis. Scar formation can be seen in some tumor tissues and cause pleural shrinkage on the lung surface. (2) Multiple nodule type: The tumor forms multiple nodules of different sizes, which are distributed in one lobe or multiple lobe. (3) Diffuse type (or pneumonia type): It is common in mucinous bronchioloalveolar carcinoma. The tumor tissue involves several lung lobes or bilateral lungs. The lesions are hard and the imaging examination is similar to lobar pneumonia.

Yang Yue	(Chief physician)	Department of Thoracic Surgery, Peking University Cancer Hospital
Wang Yuzhao	(Attending physician)	Department of Thoracic Surgery, Peking University Cancer Hospital

Bronchoalveolar carcinoma is a special subtype of lung adenocarcinoma, which accounts for about 3% to 30% of the entire non-small cell lung cancer. Compared with other non-small cell lung cancer subtypes, bronchioloalveolar carcinoma has unique clinical manifestations, tissue biological behavior, epidemiological characteristics, and special treatment response and prognosis. With the deepening of people's understanding, this concept has gradually become clear and perfect. Until 1999, the World Health Organization strictly defined bronchioloalveolar carcinoma as a lung cancer that spreads scaly along the alveolar structure without stroma, blood vessels, and pleura. This definition is still in use today. In actual cases, bronchioloalveolar carcinoma is often mixed with other types of adenocarcinoma.

Western Medicine Name: Bronchioloalveolar carcinoma
English name: bronchioloalveolar carcinoma, BAC
Affiliated Department: Internal Medicine-Respiratory Medicine

Disease site: lung
Multiple groups: female
Contagious: Non-contagious

Classification of bronchioalveolar carcinoma diseases

Causes of bronchioloalveolar carcinoma

Existing evidence suggests that the etiology of bronchioloalveolar carcinoma may be different from other types of lung cancer. For example, bronchioloalveolar carcinoma is associated with smoking, but is less relevant than other types of lung cancer. There are also reports that old scars caused by lung parenchymal damage caused by various reasons can develop into bronchioloalveolar carcinoma, such as pulmonary fibrosis, tuberculosis, pulmonary abscess or infarction. In addition, congenital cysts of the lung, some connective tissue diseases, etc. are all related to the incidence of bronchioloalveolar carcinoma. In addition, the high incidence of women may be related to carcinogens in the kitchen dust or damage to peripheral bronchioles and alveoli. The study also found that the occurrence of bronchioloalveolar carcinoma may be related to the infection of a sheep retrovirus.

Pathological characteristics of bronchioloalveolar carcinoma

The characteristics of bronchioloalveolar carcinoma under light microscopy include: (1) Tumor cells grow in scales on the alveolar wall and do not invade interstitial, blood vessels and pleura. (2) Alveolar septal sclerosis and widening, but usually no tumor-promoting fibrous tissue hyperplasia response or a large number of inflammatory cell infiltration changes. (3) Most tumor cells are well differentiated, and their morphological characteristics vary according to the origin cells.

Mucus type : composed of well differentiated, similar morphology, non-cilia, high columnar mucus-like cells. The nucleus morphology of tumor cells is relatively consistent, small in size, and located at the base of the cell base. Sometimes, nuclear heteromorphism is obvious, nucleoli are visible, and nuclear staining is deep. The cytoplasm is transparent or foamy, and mucus staining is positive. A large number of mucus components can be seen in the alveolar cavity of the lesion, and neutrophils and macrophages phagocytosing mucus are common in mucus. The interstitial lung usually does not change significantly, and there is no inflammatory cell infiltration.

Non-mucinous type: The tumor cells are well differentiated, showing a cubic or low columnar shape, and they grow in scales along the original alveolar structure. The morphology of the cells is more consistent. The cytoplasmic eosinophilic staining is obvious. The nucleus is located in the center or basal part of the cell. Tumor cells with Clara cell differentiation can be in the form of protruding and enlarged cytoplasm, and the nucleus is also located in the enlarged and protruding part to form a spike-like feature. The alveolar wall of the tumor tissue site is usually slightly thickened, and part of it is sclerosing thickening of the alveolar septum. Tumor stroma often contains a small to moderate amount of lymphocytes and plasma cell infiltration. The lymphocytes are mainly T cells, and Langerhans cells can also be seen.

Mixed type: The tissue structure and cell morphology are roughly the sum of the above two pathological types.

Clinical manifestations of bronchioloalveolar carcinoma

Compared with other types of lung cancer, bronchioloalveolar carcinoma is more common in women. Some data show that 50% to 70% of patients with bronchioloalveolar carcinoma are women, while the proportion of women in squamous cell carcinoma and other types of adenocarcinoma is only 27% and 44%, respectively. In addition, although some data show that the incidence of bronchoalveolar cancer in Asian populations appears to be higher than in European and American populations, there is no large-scale accurate data to confirm this argument.

Bronchoalveolar carcinoma is a tumor with low malignancy, inactive tumor biological behavior, and relatively slow development. Most patients are asymptomatic at early detection, mostly accidentally found during physical examination or examination of other diseases. Some patients' tumors remained unchanged after many years of follow-up, and they were finally diagnosed as bronchioloalveolar carcinoma due to surgical resection. There are also symptoms of cough, sputum, hemoptysis, chest pain, fever and dyspnea, of which cough is most common in the clinic. Compared with other types of non-adenocarcinoma, patients with multi-nodular bronchioloalveolar carcinoma have relatively large sputum volume. With the development of the disease, dyspnea may also become one of the prominent symptoms of patients. This manifestation is more common in diffuse bronchioloalveolar carcinoma, which is the only primary lung cancer that can cause progressive dyspnea.

The clinical manifestations of patients with distant metastasis are related to the site of metastasis. A large amount of clinical data shows that in advanced bronchioloalveolar carcinoma, tumor cells spread along the airways in the lungs and local lymph node infiltration is the main, and the lungs are the most common metastatic sites. Bronchoalveolar carcinoma rarely occurs in extra-pulmonary metastases, especially liver and brain metastases. In addition, bronchioloalveolar carcinoma can also produce pulmonary hypertension. Clinical manifestations such as pneumothorax and pericardial tamponade.

Bronchoalveolar carcinoma also produces two more specific manifestations. One refers to the amount of sputum produced daily> 100ml, which means bronchial fluid overflow. It has been reported that the incidence of bronchoalveolar fluid leakage in bronchioloalveolar carcinoma is mainly 6%, which is mainly seen in advanced mucinous bronchioloalveolar carcinoma. Diffuse bronchioloalveolar carcinoma can also manifest as bronchial fluid overflow, which can lead to dehydration and electrolyte disturbances. The second type is refractory hypoxemia, which is mainly found in mucinous and diffuse bronchioloalveolar carcinoma. This is mainly because the alveoli are filled with tumor cells and mucus, which results in imbalance of pulmonary ventilation and blood flow.

Bronchioalveolar carcinoma adjuvant examination

CT CT imaging findings of bronchioloalveolar carcinoma

Solitary nodular type: Histology is mostly non-mucinous. The lesions are mostly located in the upper lobe of the lungs and are common under the pleura in the periphery of the lung field. They are mostly small patchy or nodular masses with irregular shapes and can have basic CT signs of general lung cancer, such as defoliation, burrs, and pleural depression Signs and vascular bundles. In addition, nodules often appear as ground glass-like shadows, vacuole signs, and bronchial inflation signs. Ground glass shadow, or halo sign, is the density of the whole tumor nodule or nodule area is lighter than ground glass. The vacuole sign and bronchial inflation signify small focal light-transmitting areas or air-containing cavities in the nodule, which are irregular in shape, and sometimes in strips or sacs of varying widths. The pathological basis is that the tumor contains normal lung tissue or the eroded bronchus has not been completely destroyed. ^[1]

Consolidated type: The histological type of this type is mostly mucus. The pathological basis is that tumor mucus cells grow along the alveolar wall lining, and secrete a large amount of mucus to fill the alveolar cavity, resulting in pulmonary consolidation. Due to mucus secretion, the volume of the lung lobe increases and the interstitial fissure swells, which has a certain space effect. Tumors generally do not invade the interstitial lung, and the blood vessels and bronchial structures in the lung tissue can be retained for a long time. The lesions are often distributed according to the lung lobe and segments, involving one or more lung lobe segments. In addition to the frequent signs of bronchial inflation and ground glass, angiographic signs and honeycomb signs can also appear. Angiographic signs are CT-enhanced scans that clearly show high-density enhanced pulmonary angiograms in a low-density lung background. The honeycomb sign is uneven density in the lesion area, showing a honeycomb low-density cavity, different sizes, and a circular or oval shape.

Diffuse or multi-nodular type : Most of the tissue types are mucus, but also mixed. CT showed extensive miliary nodules in the lungs, about 2 to 3 mm in size, distributed in the middle and lower lobe. Both lung nodules are symmetrical or asymmetrical, and the nodule parts can be fused with each other. The morphology and imaging characteristics of each nodule can be similar to isolated nodular lesions. The larger ones can appear burrs, lobes, and pleural depressions. Part of the nodules can have flocculent ground glass or small pieces of consolidation. Shadow.

PET-CT Diagnostic value of PET-CT in bronchioloalveolar carcinoma

PET-CT is currently the most advanced and reliable imaging examination to identify benign and malignant lung solid tumors. It is also of great value in determining the whole-body TNM stage of lung cancer and judging the recurrence of lesions.

The diagnostic value of bronchoalveolar carcinoma in PET-CT is different from other types of lung cancer. For isolated nodular bronchioloalveolar carcinoma, due to the longer tumor doubling time and slower tumor cell proliferation, FDG uptake in non-small cell lung cancer depends mainly on cell proliferation, so its FDG uptake value is higher than other The type of lung cancer is significantly reduced, making PET-CT a lower detection rate for most bronchioloalveolar carcinomas, and it has been reported that the false negative rate is as high as 60%. Therefore, patients with high CT suspicion of bronchioloalveolar carcinoma and PET negative should actively perform histopathological diagnosis by fine needle aspiration or thoracoscopy, or follow up closely to observe the changes in lesion size and density.

Pathological diagnosis of bronchioloalveolar carcinoma

The "gold standard" for bronchoalveolar carcinoma diagnosis is pathological diagnosis. Sputum cytology is currently the simplest and most convenient non-invasive examination to obtain tumor specimens. The test method is to take a sputum after deep cough for three consecutive days in the morning for cytology smear examination. However, according to the latest WHO diagnostic criteria, sputum cytology is not sufficient to diagnose bronchioloalveolar carcinoma. For local, peripheral, and nodular lesions, cytology of sputum or bronchial lavage fluid has little diagnostic significance. Not only that, the strict definition of bronchioloalveolar carcinoma often requires a complete surgical resection to make a precise diagnosis to exclude the infiltration of cancerous tissue. Small biopsy specimens, such as fiberoptic bronchoscopy or percutaneous biopsy, sometimes have histological characteristics of bronchioloalveolar carcinoma, but they have not been fully diagnosed as bronchioloalveolar carcinoma. Only "adenocarcinoma, bronchioles Alveolar cancer may be diagnosed.

Differential diagnosis of bronchioloalveolar carcinoma

Radiologically isolated bronchioloalveolar carcinoma needs to be distinguished from tuberculosis, inflammatory pseudotumor, focal infection, lymphoma, hemorrhagic lesions, and organizing pneumonia; solid bronchioloalveolar carcinoma needs to be compared with lobar pneumonia , Pulmonary infarction, caseous pneumonia, lymphoma-like granuloma, chronic fibrous cavitary tuberculosis, and pulmonary interstitial fibrosis. Diffuse multinodular bronchioloalveolar carcinoma needs to be distinguished from blood-type disseminated pulmonary tuberculosis, pulmonary metastases, and lung abscesses.

Treatment of bronchioloalveolar carcinoma disease

If complete resection is available, bronchioloalveolar carcinoma with isolated lesions and multiple nodular lesions in the same lobe or on the same side of the lung should be actively treated. For pure bronchioloalveolar carcinoma after complete resection, adjuvant chemotherapy and adjuvant radiation therapy are not recommended. Radiotherapy should be the first choice for isolated or locally recurrent bronchioloalveolar carcinoma with a single lesion that is not suitable for surgery. For advanced bronchioloalveolar carcinoma that cannot be surgically removed, chemotherapy is still worth considering as a first-line treatment option for starvation. Although it is traditionally believed that bronchioloalveolar carcinoma is not sensitive to chemotherapy, the results of retrospective studies and small-scale prospective studies show that there is no statistical difference in the efficacy of chemotherapy between bronchioloalveolar carcinoma and other types of non-small cell lung cancer. Significant, but there is a feature that needs attention: the effectiveness of chemotherapy for bronchioloalveolar carcinoma is indeed lower than other types of non-small cell lung cancer, but its survival is longer than other types of non-small cell lung cancer.

For advanced bronchioloalveolar carcinoma, EGFR TKI first-line treatment can be used. SWOG 0126 clinical trial results show that Gefitinib is effective in treating bronchioloalveolar carcinoma with a 16% effective rate and a median survival time of 12 months. Another Kris study also showed that Erlotinib was effective in treating 78 cases of bronchioloalveolar carcinoma with a median survival rate of more than 12 months. The efficacy of EGFR TKI is significantly related to the EGFR mutation, which is more common in Asian populations, women, non-smokers, and patients with adenocarcinoma. The EGFR mutation rate of adenocarcinoma patients in Mainland China is 43%, which is much higher than the 10% of European and American patients with non-small cell lung cancer. Some scholars believe that the mutation rate of EGFR mutations in bronchioloalveolar carcinoma-related adenocarcinoma is higher, and EGFR targeted therapy is also found in pure non-mucinous bronchioloalveolar carcinoma and adenocarcinoma with bronchoalveolar carcinoma as the main component. Higher response rate. However, some scholars have pointed out that the EGFR mutation rate of pure bronchioloalveolar carcinoma is lower than that of adenocarcinoma with characteristics of bronchioloalveolar carcinoma, and the effective rate of TKI is much lower than that of adenocarcinoma with bronchioalveolar carcinoma. It can be seen that such an diametrically opposed view shows that this is still an area that needs further exploration.

Prognosis of bronchioloalveolar carcinoma disease

Simple bronchioloalveolar carcinoma accounts for only 4% of all non-small cell lung cancers, and more than 20% of non-small cell lung cancers contain bronchioloalveolar carcinoma components. Adenocarcinoma is a subtype of mixed bronchioloalveolar carcinoma that accounts for all adenocarcinomas. 50%. It has been found that the overall prognosis of adenocarcinoma containing bronchioloalveolar carcinoma components after TNM staging is significantly better than other types of lung cancer. In stage / adenocarcinoma, the more bronchioloalveolar carcinoma components in the tumor tissue, The better the prognosis. According to the lung cancer pathology standards established by the WHO in 1999, the 5-year survival rate of bronchoalveolar carcinoma that can be surgically removed is 70 to 100%. The prognosis of women and non-smokers is better. Ages older than 60 years, weight loss and more sputum are the negative prognostic factors. In imaging, the proportion of ground glass shadow of peripheral lesions seems to be closely related to the prognosis. Some studies have found that the survival time of patients with ground glass shadow larger than 50% of the tumor area is significantly better than that of patients less than 10%. In addition, most studies suggest that the prognosis of mucinous bronchioloalveolar carcinoma is relatively poor, and the non-mucinous type is better than the mucinous type, which is mainly based on the fact that mucinous bronchioloalveolar carcinoma is more progressive through airway expansion. At the molecular level, many studies have confirmed that bronchioalveolar carcinoma-associated adenocarcinomas with K-ras mutations have a poor response to EGFR-TKI and overall survival, and have poor prognosis even after receiving adjuvant chemotherapy. Therefore, K-ras mutation is a poor indicator of prognosis. ^[2-3]

Bronchial alveolar cancer expert opinion

The new staging of lung cancer has actually defined pure bronchioloalveolar carcinoma as a carcinoma in situ category, emphasizing that tumors cannot invade interstitial, blood vessels, and pleura. In clinical work, lung cancer with characteristics of bronchioloalveolar carcinoma is often divided into three types: simple bronchioloalveolar carcinoma, bronchioloalveolar carcinoma with local infiltration, and adenocarcinoma with bronchioalveolar carcinoma. These three types of lung cancer have basically similar clinical processes, that is, relatively long survival time, higher intrathoracic recurrence, less distant metastasis, and prone to second primary lung cancer. The more ingredients, the better the prognosis.