Bronchoalveolar carcinoma（BAC）had been a classical subtype of lung adenocarcinoma for over 50 years. However，in 2011，the International Association for the Study of Lung Cancer，the American Thoracic Society and the European Respiratory Society（IASLC/ATS/ERS）recommended replacing the term BAC with some new terminologies together to settle the abuse of the former term BAC. We think that it is hasty that this term BAC has been dropped by the IASLC/ATS/ERS. Here，we will review the history of BAC and summary its unique characteristics. Moreover，we will introduce the personalized therapy for lung cancer，including different flow diagrams for different representations on CT，which could be realized on the basis of the existence of the term BAC. Time tries truth，let's try to see whether the “revolution”for the classification of lung adenocarcinoma should be properly.

Bronchioloalveolar carcinoma（BAC），as a term of lung adenocarcinoma，was first coined by Liebow AA in 1960 ^［1］. However，even before Liebow AA，Malassez L ^［2］and Ewing J ^［3］had described the similar histological types which are considered to be BAC in 1876 and 1919，respectively. In the first edition of World Health Organization（WHO） classification of lung tumours in 1967 ^［4］，BAC was one of the two subtypes of lung adenocarcinoma，including mucinous and non-mucinous BAC. After the revisions of 1999 ^［5］and 2004 ^［6］WHO classification of lung tumours，pure BAC was to be restricted to lesions with lepidic growth without evidence of stromal，vascular，or pleural invasion，with respect to adenocarcinoma with BAC features should be diagnosed with mixed type.

It appears to be that it was stable that the status of the designation BAC in the classification of lung tumours was. Whereas，the International Association for the Study of Lung Cancer，the American Thoracic Society and the European Respiratory Society（IASLC/ATS/ERS）recommended replacing the former term BAC with some new terminologies together in 2011 ^［7］［Table 1］，for the reason that the abuse of the term BAC had confused many reviews and editorials in the clinical and research arenas. Yet the new concepts have not been adopted by the WHO officially until now.

At the moment，supported by the research of morphology，immunohistochemistry and molecular biology，it is thought that the development of the peripheral adenocarcinoma of lung follows a stepwise progression ^［8-10］，similar to the adenoma-carcinoma sequence of colorectal cancer ^［11］. Starting from a precancerous lesion，called Atypical Adenomatous Hyperplasia（AAH），to pure Bronchioloalveolar Carcinoma（BAC），regarded as the adenocarcinoma in suit according to the strict definition of the 2004 WHO classification，to mixed type Adenocarcinoma，in the end，the invasive Adenocarcinoma. AAH is the most commonly found，through the pathology examination for the specimens，adjacent to resected invasive lung adenocarcinomas ^［12］. Though AAH being regarded as the precursor lesion of lung adenocarcinoma is well recognized，the progression rate of AAH to invasive adenocarcinoma，and whether this lesion may regress remain unclear ^［13］. Through the analysis of 236 cases，Noguchi et al. delineated the model of the linear multistep progression visually by classifing small adenocarcinoma of lung into 6 types，A through F，in 1995 ^［14］.

Most lung adenocarcinoma locates in the peripheral lung，radiological findings reveal the main manifestation of most lung adenocarcinoma are nodules measuring 2 cm or less in diameter （also known as small peripheral lung adenocarcinomas），including solitary nodule and multiple nodules in one patient，while the rest manifest a pneumonic-type ^{［15，16］}. AAH and Adenocarcinoma in suit（AIS，former pure BAC）most typically manifests as a groundglass opacity（GGO），while minimally invasive adenocarcinoma （MIA，former mix type adenocarcinoma）is more likely present as a part-solid nodule and invasive adenocarcinoma is usually visible as a solid nodule，which indicate that the emerging solid component among the GGO may represent the existence of invasive tumors ^［17］. Soda et al. described a case with lung adenocarcinoma in which GGO transformed through a scar-like lesion over the long term into a solid nodule of poorly differentiated adenocarcinoma over 54 months of follow-up ^［18］.

BAC has been well known as a unique subset of lung adenocarcinoma with distinctive pathologic and clinical features，although we haven't been able to characterize it exactly. Overwhelming studies give us a glimpse of its biological characteristics. Firstly，the growth of BAC is usually slow，Chang et al. found that the median volume doubling time was 769 days for growing screening-detected pure GGO nodules，meanwhile，rare lymph node metastasis was recognized ^{［19，20］}. Then，another unique feature of BAC is its tendency to present as multiple foci within the lung parenchyma，indicating that they are more likely to be synchronous primary nodules，rather than intrapulmonary metastasis ^{［21，22］}. Third，the 5-year cancer-specific survival rate after limited resection for AIS and MIA，i.e. Noguchi's type A and B，is almost 100% ^{［19，23］}. In addition，a sheep lung cancer，which is similar to human bronchioloalveolar cancer，now is clarified that caused by Jaagsiekte Sheep Retrovirus（JSRV），has aroused the extensive interest in the viral aetiology for BAC ^［24］.

Thus，there are 3 different presentations of CT findings：1）a solitary nodule or mass of varying density；2）focal consolidation；and 3）multifocal or diffuse disease ^［25］.

The lack of symptoms in patients with lung adenocarcinoma leads to the promotion of lung cancer screening program，such as chest radiography，sputum cytology，low dose computed tomography（LD-CT），and exhaled breath analysis ^［26］. Recently，low-dose computed tomography（LD-CT） has been widely used for lung cancer screening and proved to be a favorable method for improving 10-year survival of patients with lung cancer，and most peripheral lung cancer detected by LD-CT were，presenting as nodules，small peripheral lung adenocarcinomas ^［27-29］.

The only potential curable therapy for lung cancer is surgery. However，the appropriate management of nodular pulmonary adenocarcinoma has not been clearly defined. Nodular pulmonary adenocarcinoma should be classified as uni- and multinodular according to the number of nodules，meanwhile，sorted by density into GGO，part-solid and solid nodules. Here，we will review the treatment for nodular pulmonary adenocarcinoma by reference to the imaging manifestation and therapy for BAC.

Numerous studies focused on demonstrating the the different 5-year survival rates after surgery among various density pulmonary nodules. Noguchi et al. found the overall 5-year survival rate among small peripheral lung adenocarcinoma after surgery is 74.9%，similiar to the Noguchi type C，while the type A and type B is almost 100%，type D is 52% ^［14］. Asamura et al. studied a 10-year period from 1991 through 2000 a total of 1，769 lung tumors were resected at the National Cancer Center Hospital，Tokyo and found that among subcentimeter lung cancers，GGO lesions（both non-solid and part-solid）constitute true early lung cancers ^［30］. Ebright et al. thought Clinical pattern and pathologic stage but not histologic features predict outcome for bronchioloalveolar carcinoma，indicating the potential unique behavior of BAC ^［22］. Vazquez，M.，et al. thought the proportion of BAC component was a positive prognostic factor and correlated with CT consistency，through examination of the histopathologic features of CT screendetected stage IA adenocarcinomas in 279 resected cases ^［31］. Higashiyama et al. assessed 206 consecutive cases of surgically resected small peripheral lung adenocarcinoma（less than 2 cm in diameter），they semiquantitatively classified the tumors into four types：in which the BAC component comprised 0%（type Ⅰ），1% to 49%（typeⅡ），50% to 99%（typeⅢ），and 100%（type Ⅳ）of the tumor tissue，found that the tumors with less BAC，especially type I and Ⅱ，showed worse prognosis ^［32］.

The rigorous obtainment of those statistic data is strongly associated with the appropriate surgical treatment. Currently，The standard surgical treatment for patients with non-small-cell lung cancer（NSCLC）is lobectomy with systematic nodal dissection （SND） ^［33］. Minimal invasive surgery is an excellent approach for the diagnosis and treatment of lung cancer，and the direction of the development of surgery towards the more minimal invasive surgery. Minimal invasive thoracic surgery is not only from open thoracotomy to video assisted thoracoscopic surgery（VATS）or uniportal VATS，but also may be less resection of lung parenchyma and less removed Lymph nodes. Less resection of lung parenchyma means more pulmonary function reserved. Furthermore，it may preserve sufficient lung parenchyma to resect in case of recurrence，which is not rare for lung cancer. Based on this idea，scholars with exploring spirit are doing innovative studies on the surgical treatment of early-stage lung cancer. Limited resection，including segmentectomy，sublabar resection and wedge resection，may be potential substitute for lobectomy. Thanks to the unique characteristics，BAC may be an excellent potential indication for limited resection. The results of a prospective phase Ⅱ study by Koike et al. indicate that limited resection，mainly by wedge resection，is a potentially curative surgical procedure and may be an acceptable alternative to lobectomy for patients with noninvasive BAC ^［19］. To examine whether segmentectomy is radical for cT1N0M0 non-small cell lung cancer（NSCLC），Nomori et al performed a prospective study for patients with selected cT1N0M0 NSCLC，found that segmentectomy with systematic lymph node dissection with a sufficient surgical margin could be a radical treatment for selected cT1N0M0/pN0 NSCLC while preserving pulmonary function ^［23］. Lung cancer is a difficult disease to treat，those sublobar resections for lung cancer leaded to thinking about the personalized lung cancer resection. There are 3 major prospective trials，CALGB140503，JCOG0804 and JCOG0802，are ongoing. A scientific comparison of the prognosis between lobectomy and limited resection for early stage lung cancer is the main aim of those trials，and an active outcome is now believed. As for the most appropriate procedure for lymph node excision，results of the American College of Surgery Oncology Group Z0030 Trial（ACSOG Z0030）partly clarified that if systematic and thorough presection sampling of the mediastinal and hilar lymph nodes is negative，mediastinal lymph node dissection does not improve survival in patients with early stage non-small cell lung cancer，in which sampling of lymph nodes means patients with non-small cell lung cancer underwent sampling of 2R，4R，7，and 10R for right-sided tumors and 5，6，7，and 10L for left-sided tumors ^［34］. In addition，lobe-specific symtematic nodal dissection has been proposed by several scholars. Through examination of 282 patients with early lung cancer，Shapiro et al. found that lobespecific mediastinal nodal dissection is sufficient during lobectomy by video-assisted thoracic surgery or thoracotomy for early-stage lung cancer ^［35］. However，Maniwa et al. thought the recurrence of mediastinal node cancer in patients undergoing L-SND was significantly greater than that in those undergoing SND in 129 cases ^［36］. In a word，although a variety of trials are in full swing，lobectomy with SND still be the typical surgical treatment for early stage lung cancer，currently.

However，with the progress of the screening programs for lung cancer，here comes some other problems，more and more patients with solitary pulmonary nodule have been detected. How to identify which pulmonary nodules are malignant effectively？ Whether standard surgical procedure is urgently needed among all those patients？ How patients should be follow-up if doctors think surgery is not needed for the moment？ Personalized perioperative therapy and surgery personalization by tumor subtype is urgently needed. We recommend the flow-process diagram for detected solitary pulmonary nodule . The diagram may contribute to the individualized and standardized clinical treat for solitary pulmonary nodule if use flexibly.

Among nodules within a patient，it is difficult，but very important，to identify whether those nodules are synchronous or metachronous foci of malignancy. The latest 7th TNM system for lung cancer stages cases with multiple nodules as T3 or T4 depending on their location in the same or different lobes unilaterally，while stage bilateral cases as M1a ^［37］. According to the current TNM system，these additional nodules are primarily identified as isolated pulmonary metastases，and patients with multiple nodules should be treated as advanced stage. However，The analysis of International Association for the Study of Lung Cancer International Database indicated that current TNM system of lung cancer remains insufficiently discriminatory of future patient outcomes，for example，the 1-year survival for cM1acontralateral nodule and cM1b-single site were 45% versus 23% ^［38］. Yu et al. thought tumor size was the only independent prognostic factor for synchronous multiple primary lung cancers with surgical intervention，not the current TNM classification system ^［39］.

Nonmucinous bronchioloalveolar carcinoma has its tendency to represent as multifocal，independent cancers，recognized GGO lesions when detected by CT. Kim et al. revealed that close follow-up using CT scans could substitute for surgical resection for multiple pure ground-glass opacity lesions in patients with bronchioloalveolar carcinoma，for the reason that no GGO lesions increased in size or developed a solid component during their follow-up period ^［40］. International Early Lung Cancer Action Program（I-ELCAP）recommended that cases of nonsolitary adenocarcinoma without evidence of lymph node or distantmetastases，even if both were of the same histologic subtype，should be treated as stage I lung cancer ^［31］. In 1975，Martini and Melamed proposed the so-called M-M criteria to try to distinguish primary multiple nodules from metastasis ^［41］. But it remains difficult to solve this problem until now. Prior to an official flow-process diagram，we drawn up a treatment strategy for multiple lung cancers in accordance with our clinical practice.

Consolidative lung cancer，also known as pneumonic-type lung cancer，has been regarded as the true advanced stage lung cancer with higher degree of invasion and poorer prognosis，and the difuse BAC could present with lung consolidation. Palliative pneumonectomy is the major method to relief patients' pain and extent their life as much as possible. Fabrice et al. reported four patients with bilateral bronchioloalveolar lung carcinoma to receive palliative pneumonectomy，one died immediately after the surgical procedure，while other 3 patients got 10 months improved control of respiratory symptoms and more than 18 months survival ^［42］. When moving to the end-stage，lung cancer could be surgical treated with pulmonary transplantation beside chemoradiotherapy and targeted therapy. According to an analysis for the United Network for Organ Sharing Registry in 2012，survival after lung transplantation for BAC appears to be consistent with that of lung transplantation for other diagnoses and is better than that reported with chemotherapy ^［43］.

Bronchoalveolar carcinoma（BAC）had been long well recognized as a pathological histology subtype of lung adenocarcinoma with distinct clinical presentation，tumor biology，response to therapy and prognosis for over 50 years. Novel IASLC/ ATS/ERS multidisciplinary classification replaced BAC with several new pathological terms on the basis of their reasonable consideration：to resolve the ongoing discrepancy in the pathologic vs clinical use of the term BAC. In fact，there exists chaos in practice because of the abuse of the term BAC. There would be a tendency to adopt the alternative new terms in the literature published recently in spite of the WHO doesn't accept the new multidisciplinary classification officially until now. In contrast，Xu et al. wondered whether the term is really dead？ However，their theme focused on the lack of clarity regarding what constitutes true invasion in well-differentiated lung adenocarcinomas，and if the use of a 5 mm limit is workable or if the term ‘LPA' has traction ^［44］.

Nowadays，thoracic surgery moves forward to more minimally invasive，and personalized perioperative therapy and surgery personalization by tumour subtype is a promising direction. Several major prospective randomized controlled trials are ongoing，turning out，thanks to the distinct unique chracteristics of BAC，that BAC may be the most potential subtype to perform those experiments. Obviously，early stage lung cancer is more likely to be cured by surgical procedure than advanced stage. Thus，the contents of true early stage lung cancer should be well defined. BAC could be，and in fact it has been now，the fruit flies or the broad beans within the studies for personalized surgery，including perioperative program，the range of pneumonectomy，the extent of lymph nodes removed，etc. Time will tell us whether the classic BAC should be back to the classification of lung adenocarcinoma.

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