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Pulmonary Pathology Online

Pathology of Adenocarcinoma In Situ and Minimally Invasive Adenocarcinoma (Previously known as Bronchioloalveolar Carcinoma)

 Dr Sampurna Roy MD




 Adenocarcinoma In Situ and minimally invasive adenocarcinoma are new terms to decribe what was previously known as Bronchioloalveolar Carcinoma (BAC)

The terms BAC is no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) or predominant lepidic growth with ≤ 5 mm invasion (MIA) to define patients who, if they undergo complete resection, will have 100% or near 100% disease-specific survival, respectively.

AIS and MIA are usually nonmucinous but rarely may be mucinous. Invasive adenocarcinomas are classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous BAC), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype.

Variants include invasive mucinous adenocarcinoma (formerly mucinous BAC), colloid, fetal, and enteric adenocarcinoma.

This classification provides guidance for small biopsies and cytology specimens, as approximately 70% of lung cancers are diagnosed in such samples.

Adenocarcinoma In Situ (AIS) is an uncommon form of adenocarcinoma of the lung with unique pathological, clinical, and molecular characteristics.  

The tumour arising in the terminal bronchioloalveolar regions is almost always located in the lung periphery.

Clinically, they occur in men and women equally and are not usually associated with smoking.

Grossly these are single or multiple nodules or a diffuse pneumonic consolidation with tumour.

In cases in which the tumor presents as a solitary nodule, the size of the lesion is of importance.

Tumors measuring less than 0.5 cm in greatest dimension are best categorized as examples of atypical adenomatous hyperplasia, a benign lesion that is believed to be a possible precursor to BAC.

Older Classification classification Bronchioloalveolar Carcinoma:

The two histologic subtypes: 

1. Mucinous type- Mucinous bronchioloalveolar carcinomas are now called "Invasive mucinous adenocarcinoma." Proliferation of fairly uniform columnar mucin-secreting cells which replace the normal alveolar lining.  

2. Non-mucinous type- Characterized by round to cuboidal cells with scant cytoplasm and prominent, hyperchromatic nuclei which often adopt a "hobnail" appearance.   

Histologically, the tumour is distinctive in that tall columnar, often mucin-producing tumour cells line up along preserved alveolar septa, forming papillary projections within the spaces. 

Updated: Adenocarcinoma In Situ (AIS) ; Minimally invasive adenocarcinoma (MIA) and Invasive Mucinous adenocarcinoma:

"To qualify as a AIS , the tumour must not show any evidence of infiltration of the stroma or adjacent lung parenchyma or the pleura, or lymphatic spread to lymph nodes.

The tumour has a distinctive growth pattern, the so-called lepidic pattern, in which the tumour cells line the alveolar walls and appear to gradually replace the normal lining epithelium of the airspaces while preserving its basic architecture. 

Tumours showing the characteristic lepidic growth pattern of AIS but that also show, even if focally, infiltration of either the lung parenchyma or the pleura are currently categorized as  MIA"

Mucinous bronchioloalveolar carcinomas are now called "Invasive mucinous adenocarcinoma".

The entire lesion should be examined for assessment of invasion.

It is no longer possible to make a diagnosis of BAC on cytological specimens or on small endoscopic or percutaneous needle biopsy specimens.

Cytologically, BAC may be composed of 2 different cell types, one characterized by mucinous epithelium and the other by nonmucinous epithelium composed of small cuboidal cells with scant cytoplasm and hyperchromatic nuclei, the "hobnail" pattern.


Further reading:

Reclassification of early stage pulmonary adenocarcinoma and its consequences.

The new 2011 international association for the study of lung cancer/american thoracic society/european respiratory society classification of lung adenocarcinoma in resected specimens: clinicopathologic relevance and emerging issues.

The 2011 IASLC/ATS/ERS pulmonary adenocarcinoma classification: a landmark in personalized medicine for lung cancer management.

The IASLC/ATS/ERS classification of lung adenocarcinoma-a surgical point of view.

Managing multifocal bronchioloalveolar carcinoma/lepidic predominant adenocarcinoma: changing rules for an evolving clinical entity.

Bronchioloalveolar carcinoma of mixed mucinous and nonmucinous type: immunohistochemical studies and mutation analysis of the p53 gene.

Comparison of the immunophenotypes of signet-ring cell carcinoma, solid adenocarcinoma with mucin production, and mucinous bronchioloalveolar carcinoma of the lung characterized by the presence of cytoplasmic mucin.

Multiple bronchioloalveolar carcinomas in acromegaly: a potential role of insulin-like growth factor I in carcinogenesis.

Bronchioloalveolar carcinoma and lung adenocarcinoma: the clinical importance and research relevance of the 2004 World Health Organization pathologic criteria.

Misclassification of bronchioloalveolar carcinoma with cytologic diagnosis of lung cancer.

Bronchioloalveolar carcinoma of the lung 3 centimeters or less in diameter: a prognostic assessment.

Immunohistochemical analysis of lung carcinomas with pure or partial bronchioloalveolar differentiation.

Usefulness of Cdx2 in separating mucinous bronchioloalveolar adenocarcinoma of the lung from metastatic mucinous colorectal adenocarcinoma.

Emerging approaches to advanced bronchioloalveolar carcinoma.

From cystic pulmonary airway malformation, to bronchioloalveolar carcinoma and adenocarcinoma of the lung.

Lung adenocarcinoma with mixed bronchioloalveolar and invasive components: clinicopathological features, subclassification by extent of invasive foci, and immunohistochemical characterization.

Reclassification of cystic bronchioloalveolar carcinomas to adenocarcinomas based on the revised World Health Organization Classification of Lung and Pleural Tumours.

Expression of cytokeratin 20 in mucinous bronchioloalveolar carcinoma.

Clinical pattern and pathologic stage but not histologic features predict outcome for bronchioloalveolar carcinoma.

Stage I pure bronchioloalveolar carcinoma: recurrences, survival and comparison with adenocarcinoma of the lung.

Comparative analysis of clinical features and prognostic factors in resected bronchioloalveolar carcinoma and adenocarcinoma of the lung.




Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)







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