Daly et al. evaluated presenting symptoms of 134 patients diagnosed with BAC. Of those, 68% were asymptomatic at presentation with 17% presenting with a cough. Unlike other NSCLCs, bronchorrhea or excessive airway secretions were more common in this subgroup (17%) as was nonspecific chest pain (10%). Copious frothy secretions up to a few liters per day have been reported to the extent of causing a fluid-electrolyte imbalance. Its presence usually portends a poor prognosis.[9]

Routine chest x-ray findings of non-resolving pneumonia or an isolated, persistent, ill-defined opacity have often been reported as the primary starting point of diagnosis.[8][10][11]

Computed tomography (CT) of the chest may show an isolated, or more often, a multifocal or diffuse opacity with a predominant ground-glass pattern. 

Size and mass of the nodule are important predictors of an invasive component. 

Differential diagnosis of a ground glass area of opacity in CT may include organizing pneumonia, focal inflammation, or focal fibrosis. Precise measurement of a subsolid nodule size can often be challenging in axial CT. An alternative method of measurement could be volumetry though it has not been standardized and validated. 

While erstwhile non-mucinous bronchioloalveolar carcinoma presents most commonly as ground-glass nodules with a variable solid component, mucinous bronchioloalveolar carcinoma more often present as pneumonic infiltrates with consolidation, pseudo cavitation, and often visualization of blood vessels within the area of mucinous consolidation – known as " angiogram sign." 

Consolidation tumor ratio, defined as a ratio of the maximum diameter of the area of consolidation to the tumor, has also been used as a prognostic marker in the non-solid adenocarcinoma with lepidic growth.

Cellular density and turnover being somewhat lower, fluorodeoxyglucose (FDG) uptake in a positron emission tomography (PET) scan is often underwhelming, and these lesions are often, therefore, PET negative.

Forty-five percent to 60% of the erstwhile bronchioloalveolar carcinomas have been reported to present in radiologic stage 1 or stage 2 disease.

Tissue diagnosis by biopsy is the confirmatory step. However complete histologic evaluation of an excised specimen or biopsy is increasingly stressed upon to determine the extent of invasiveness. The diagnosis of adenocarcinoma with lepidic growth made by cytology or core biopsy can contain a more invasive component in an excised specimen. 

The specificity of frozen section biopsy of diagnosing adenocarcinoma with lepidic growth is excellent, however, with positive predictive values of 93% to 100%.

Complete surgical excision is the most definitive therapy to align with the reported recurrence-free survival rates. Lobectomy has been the most followed approach although, in clinical practice, patients with limited lung functions or multifocal synchronous disease pose a challenge at times. Limited resection by segmentectomy or sublobar resection has, therefore, been considered under less than ideal circumstances for lobectomy.[1][12][13]

Radiologic pure solid adenocarcinoma is found to have intraoperative nodal involvement in 15% to 20% of cases, and is, therefore, not considered to be ideal candidates for sublobar resection. Hattori et al. retrospectively reviewed 200 radiologic stage 1a lung adenocarcinoma cases to identify clinical factors associated with histologic lepidic predominant adenocarcinomas. They found that SUV max level of less than 3.3 in PET scan correlated well with lepidic predominant growth even in pure solid stage 1a adenocarcinomas, and therefore opens up scope for sublobar resection in the subgroup that would not tolerate lobectomy otherwise.[14]

Differential diagnosis of bronchioloalveolar carcinoma with similar histological findings but much more favorable prognosis includes:

• Type 2 pneumocyte hyperplasia
• Atypical adenomatous hyperplasia
• Sclerosing hemangioma

Immunophenotyping is helpful in differentiation.

Early chemotherapy trials with paclitaxel in advanced bronchioloalveolar carcinoma showed a somewhat better outcome than another similar stage adenocarcinoma otherwise but poor nevertheless. Hirsch et al. demonstrated that these tumors do have a high expression of EGFR mutation, opening up a potential early therapeutic target. Two large trials (SWOG and MSKCC- VANDERBILT) demonstrated a robust response to erlotinib and gefitinib, as frontlines of therapy more often in bronchioloalveolar carcinoma patients. 

Erstwhile mucinous bronchioloalveolar carcinomas, however, are more frequently K ras mutation-positive (reported at 75%) with low expression of EGFR mutation. They are, therefore, somewhat more responsive to taxane-based chemotherapy and are not ideal candidates for EGFR targeted therapy.[15]

Finally, like other variants of adenocarcinoma, the treatment of locally advanced or metastatic adenocarcinoma with lepidic growth has also been positively impacted by the advent of immunotherapy in general, and PD1-L1 inhibitors to be specific.

• Stage 0
• TisN0M0
• Stage IA1
• T1miN0M0
• T1aN0M0
• Stage IA2
• T1bN0M0
• Stage IA3
• T1cN0M0
• Stage IB
• T2aN0M0
• Stage IIA
• T2bN0M0
• Stage IIB
• T1aN1M0  
• T1bN1M0
• T1cN1M0
• T2aN1M0
• T2bN1M0 
• T3N0M0
• Stage IIIA
• T1aN2M0 
• T1bN2M0
• T1cN2M0   
• T2aN2M0   
• T2bN2M0     
• T3N1M0   
• T4N0M0
• T4N1M0
• Stage IIIB
• T1aN3M0 
• T1bN3M0     
• T1cN3M0   
• T2aN3M0   
• T2bN3M0     
• T3N2M0 
• T4N2M0 
• Stage IIIC
• T3N3M0   
• T4N3M0
• Stage IVA
• Any T, any N, M1a or M1b
• Stage IVB
• Any T, any N, M1c      
• M1a designates metastasis within the thoracic cavity
• M1b designates a single extrathoracic metastasis M1c designates multiple extrathoracic metastases

Tumors classified as MIA and AIS have been shown to have a near 100% disease-free survival once completely resected. (100% 10-year disease-free survival for AIS and 97.3% to 100% for MIA)[16][17]

Tumors identified as bronchioloalveolar carcinoma or adenocarcinoma with lepidic growth rarely follow the traditional progression through nodal or vascular involvement. Multifocal disease within lung parenchyma has been seen and attributed to synchronous disease or aerogenous spread. Given their intrathoracic spread, even lung transplantation has been performed in cases of multifocal BACs but has often exhibited recurrence in the donor's lung as late as 48 months post-transplantation.

Considering all forms of adenocarcinoma, the solid component (contrary to ground glass) and mucinous pattern are widely considered to be predictors of metastatic potential.

The reason the name " bronchioloalveolar carcinoma" was destined to die was that it clubbed two very unrelated forms of adenocarcinoma in histology, immunophenotype and invasive nature. It also became important to recognize minimally invasive adenocarcinoma, which portends a similar prognostic significance as AIS or reclassify adenocarcinoma purely from the prognostic viewpoint. 

Since the introduction of the newer classification, there have been several articles with caution and counterarguments. The purpose of those is not to be ignored as they convey a valued message that identification of adenocarcinoma as one with lepidic growth does not label them as one with potential curability or 100% disease-free survival until a surgical staging has been achieved with adequate evaluation of the specimen in its entirety along with evaluation of pleura and lymph nodes. Finally, it has opened up scope for early planning of definitive therapy with sometimes less limited resection and preservation of lung function with equally optimistic outcomes.

Smoking cessation counselling and education are imperative with the diagnosis of this disease. Screening should be conducted in patients over the age of 50 who have the following risk factors:

• A family history of lung cancer
• Radon exposure 
• Occupational exposure to carcinogenic particles
• Chronic lung disease
• Smoking

• Radiographic evidence of resolving pneumonia or persistent ground-glass opacity should always raise suspicion for adenocarcinoma with lepidic growth. 

• Diagnosis of adenocarcinoma with lepidic growth should be avoided from pure cytology or core biopsy specimens without evaluating an entire excised specimen for an invasive component.

• The presence of invasive component excludes the diagnosis of AIS or erstwhile bronchioloalveolar carcinoma. 

• Histologic evidence of lepidic tumor growth has mirrored a uniform CT appearance of ground glass pattern, a favorable prognostic pattern and, therefore, a scope for targeted therapy as well as limited surgical resection.

• The diagnosis of AIS, MIA, and even AAH are likely to grow in the recent and coming years due to their incidental diagnosis by the National Lung Cancer Screening Trial. 

• What was previously known as mucinous bronchioloalveolar carcinoma is now recognized as invasive mucinous adenocarcinoma.

The survival of most patients with lung cancer is poor. Thus, a streamlined approach to diagnosis and treatment is recommended. the earlier the cancer is diagnosed, the higher the cure rate with surgery. Since the majority of patients with lung cancer initially present to the primary caregiver, a high index of suspicion should be held. Any patient with risk factors for lung cancer should at least have a chest x-ray and possibly a CT scan of the chest. The radiologist is essential for biopsy of any lung lesion, and the pathologist is necessary to determine the type of cancer. A thoracic surgeon should be involved in the care of the patient since early surgery is curative. Even after surgery, an interprofessional team of healthcare workers needs to follow the patient to ensure that there is no recurrence or metastatic disease.[18] [19][Level V] For those patients deemed non-surgical candidates, the treatment is chemotherapy. When metastases occur, a pain management specialist and a radiation oncologist must be consulted to determine the options for pain management. With the availability of the newer targeted agents, the oncology specialist pharmacist plays a key role in selecting agents and monitoring the patient for adverse reactions and reporting concerns to the team. There are many guidelines established to assess patients for lung cancer but the key is an index of suspicion.

BAC is managed by an interprofessional team. Besides the pulmonologist and thoracic surgeon, other team members may include a pathologist, oncologist, radiation oncologist, pharmacist, and specialty trained nurses in surgery and oncology. The surgical nurse should assist in the coordination of care, patient and family education regarding surgery, and monitoring the patient for surgical complications with reporting of untoward events to the team. Pharmacists should evaluate medications prescribed, drug-drug interactions, and patient compliance and communicate with the team. Specialty trained oncology nurses should assist with aftercare by helping with the education of the patient and their family, coordination of followups, and evaluating for recurrence and report issues to the team.[Level 5]

Outcomes

Tumors classified as MIA and AIS have been shown to have a near 100% disease-free survival once completely resected. (100% 10-year disease-free survival for AIS and 97.3% to 100% for MIA)[Level II]

Tumors identified as bronchioloalveolar carcinoma or adenocarcinoma with lepidic growth rarely follow the traditional progression through nodal or vascular involvement. Multifocal disease within lung parenchyma has been seen and attributed to synchronous disease or aerogenous spread. Given their intrathoracic spread, even lung transplantation has been performed in cases of multifocal BACs but has often exhibited recurrence in the donor's lung as late as 48 months post-transplantation. [20][1][Level II]