Adenocarcinoma in situ, minimally invasive adenocarcinoma and invasive adenocarcinoma of the lung are relatively new classification entities which replacehave replaced the the now-defunct term bronchoalveolar carcinoma (BAC).

In 2011 the International Association for the Study of Lung Cancer (IASLC) and several other societies jointly revised the classification for adenocarcinoma of lung ¹³. The new classification strategy is based on a multidisciplinary approach to the diagnosis of lung adenocarcinoma. The terms bronchoalveolar carcinoma and mucinous and non-mucinous bronchoalveolar carcinoma have been rendered obsolete.

Terminology

Before a general discussion of the topic, it is worth highlighting some of the updated terminology and concepts, as for many who were taught the term bronchoalveolar carcinoma, some adjustment will be necessary ⁵:

• adenocarcinoma in situ of lung (AIS) (≤3 cm) has a number of subtypes
  • the most common subtype is non-mucinous and rarely mucinous or mixed subtypes
  • histological pattern: no growth pattern other than lepidic and no feature of necrosis or invasion
• minimally invasive adenocarcinoma of lung (MIA) ≤3 cm
  • describes small solitary adenocarcinomas with either pure lepidic growth or predominant lepidic growth with ≤5 mm of stromal invasion

The two invasive adenocarcinomas previously termed non-mucinous and mucinous bronchoalveolar carcinoma have been renamed:

• lepidic-predominant adenocarcinoma describes invasive adenocarcinoma with a predominant lepidic pattern with >5 mm invasion; formerly known as non-mucinous bronchoalveolar carcinoma
• invasive mucinous adenocarcinoma is a variant of invasive adenocarcinoma; formerly known as mucinous bronchoalveolar carcinoma

Epidemiology

AIS and MIA are an uncommon type of bronchial carcinoma which occurs most frequently among non-smokers, women and Asians. It is a subtype of adenocarcinoma, but has a significantly different presentation, treatment and prognosis. Adenocarcinoma in situ and minimally invasive adenocarcinoma represent between 2-14% of all primary pulmonary malignancies ¹¹. There is no significant gender predilection, unlike other lung cancer types which are more prevalent in men.

Risk factors

• a pre-existing focus of pulmonary fibrosis, e.g. tuberculosis scar, infarct, scleroderma.

Clinical presentation

Presentation is often insidious, and a large proportion (50%) of patients may be asymptomatic at the time of detection ¹. Alternatively, as these tumours can produce large quantities of mucus, patients may present with bronchorrhea.

Persistent consolidation for weeks despite appropriate antimicrobial therapy should raise the suspicion of a neoplastic process. CT or guided biopsy may be planned in such cases.

Pathology

Adenocarcinoma in situ: ≤3 cm, demonstrates a lepidic growth pattern, spreading along the walls of the lung without destroying the underlying architecture. In addition, they are characterised by the absence of stromal, vascular or pleural invasion.

Minimally invasive adenocarcinoma: ≤3 cm, describes small solitary adenocarcinomas with either pure lepidic growth or predominant lepidic growth with ≤5 mm of stromal invasion.

Three pathological subtypes are recognised ³:

• non-mucinous
• mucinous: goblet cell (mucus-secreting), often multi-centric
• mixed

Radiographic features

There are three recognised radiographic patterns ¹

• single mass or nodular form (commonest): ~45 %
• consolidative form: ~30 %
• multinodular form: ~25 %

Plain radiograph

May show segmental or lobar consolidation with chronic unilateral airspace opacification and air bronchograms. Can also present as a pulmonary nodule, mass or a cluster of diffuse nodules ^1,2. The nodular form (commonest) can be indistinguishable from another subtype of adenocarcinoma or inflammatory granuloma on plain film ¹.

CT

The appearance on CT depends on its pattern of growth; hence, it may appear as:

• a peripheral nodule
  • commonest appearance
  • typically solitary and well-circumscribed ⁵
  • the nodule may be surrounded by a halo of ground-glass opacity, the so-called fried egg sign
  • cavitation
    • pseudocavitation (presence of bubble-like lucencies) is recognised ^1,5
    • overt cavitary changes rarely occur (~7%)
    • cavitating pulmonary metastases may occur (Cheerios sign ⁹)
• a focal area of ground glass (early sign)
  • heterogeneous attenuation
• a region of ground glass, with or without consolidation
• hilar and mediastinal adenopathy and pleural effusion are uncommon
• • air bronchograms may be seen (also known as the open bronchus sign)
  • CT angiogram sign

Nuclear medicine

F-18-FDG-PET is often negative ^6,7.

Treatment and prognosis

Surgical resection is required with either lobectomy or pneumonectomy.

Overall, tumours that demonstrate only lepidic growth tend to be indolent, with high 5-year survival. However, solid, invasive components are frequently present and despite radical treatment, recurrence rates are high. Mucinous subtypes have worse prognosis ⁴, probably due to aerogenous spread that forms infiltrating, multifocal, or satellite tumours ¹¹.

History and etymology

The entity formerly known as bronchoalveolar carcinoma was first described by Malassez in 1876, as a bilateral, multinodular form of malignant lung tumour ^11,12.

The shifting terminology of non-invasive adenocarcinoma reflects both an increased utilization of immunohistochemical testing, as well as advances in personalized cancer treatment. Beginning with the 1999 World Health Organization guidelines, there has been an attempt to isolate purely non-invasive and minimally-invasive adenocarcinoma from more advanced adenocarcinoma, due to uniquely favourable prognosis in the former ¹⁴. Prior to the 2011 IASLC/ATS/ERS update, various forms of invasive disease remained lumped into the BAC category. Thus, scrapping the BAC classification was intended to further remove ambiguity.

Differential diagnosis

General imaging differential considerations are broad, so it is useful to consider differentials for specific patterns, which include:

• differential of chronic alveolar opacity
• differential of a solitary pulmonary nodule
• differential of ground glass opacity

See also

• non-small cell lung cancer
• adenocarcinoma of the lung
  • invasive adenocarcinoma of the lung