CONTENTS

5.3 ‘Minimally Invasive’ Adenocarcinoma of the lung (MIA)
5.4 Adenocarcinoma of the Lung
5.4.1 Bronchioloalveolar Carcinoma (BALC)
5.4.2 Mucinous Adenocarcinomas (non-BALC type)
5.4.3 ‘Colloid’ Carcinoma
5.4.4 Papillary Adenocarcinoma
5.4.5 Fetal Adenocarcinoma
5.4.6 Adenosquamous Carcinoma

Forward to 5C Squamous Cell, Large-Cell and Sarcomatoid Carcinoma .   Back to 5A Incidence and Classification of Lung Cancer .

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5.3 ‘Minimally Invasive’ Adenocarcinoma (MIA)

 
For resection specimens, new concepts have been introduced by the 2011 International Association for the Study of Lung Cancer  (IASLC) American Thoracic Society (ATS) and the European Respiratory Society (ERS) lung cancer classification, such as adenocarcinoma in situ (AIS), which has pure ‘lepidic’ growth (see Section 4) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with predominant lepidic growth and with ≤ 5 mm invasion (MIA).

The word ‘lepidic‘ means that the cancer cells are found in single-file along the bronchi and alveolar walls, with no invasion or papillary formations.

For patients with MIA, if they undergo complete resection, will have 100% or near 100% disease-free survival. MIA is usually non-mucinous.

5.4 Adenocarcinoma of the Lung

 
Adenocarcinoma is the most common type of lung cancer, accounting for approximately between 50 % and 60 % of lung cancer cases. Patients often present with a peripheral lung mass.

The histopathological (microscopic) diagnosis of adenocarcinoma of the lung requires observation of tumor gland formation or mucin secretion within tumor cell cytoplasm.  The morphology of cancerous glands can be varied; well-formed acini may be present, or papillary formations or cribriform collections of cells.

Histochemical stains, such as mucicarmine, Alcian Blue (AB) or Periodic Acid-Schiff (PAS) detect mucin within cells and extracellularly.

The solid variant of adenocarcinoma is less ‘well-differentiated’ and is histologically indistinguishable from ‘large cell undifferentiated’ carcinoma, except for the presence of intracellular mucin.

Invasive Adenocarcinoma of the Lung and Classification

 
Invasive lung adenocarcinomas are classified by their predominant tumor pattern on histology (microscopy). The patterns of adenocarcinoma now described histologically include:

• lepidic (formerly most mixed subtype tumors with non-mucinous BALC)
• acinar
• papillary
• solid

Variants now include:

• invasive mucinous adenocarcinoma (formerly mucinous BALC),
• colloid adenocarcinoma,
• fetal adenocarcinoma, and
• enteric adenocarcinoma.

Figure 5.2 Adenocarcinoma of the Lung.

A. Macroscopic appearance of an excised peripheral lung tumor.
B. Diagnostic fine needle aspiration cytology (FNAC) showed large
cells with prominent nucleoli and pale cytoplasm; We can see numerous
mitoses and apoptotic bodies. (PAP x 63).
C. Photomicrograph of the histology shows gland formation and
groups of infiltrating cancer cells associated with fibrosis and
inflammation. (H&E x40).

This updated classification gives some guidance for small biopsies and cytology specimens; approximately 70% of lung cancers are diagnosed in these small samples.

Sometimes, the lung tumor cannot be classified using light microscopy alone.  In this case, special studies such as histochemical mucin stains and immunohistochemistry (IHC) may be required. The new classification guidelines advise that, even in small biopsy or cytology samples, use of the terms Non -Small Cell Lung Cancer  (NSCL) and Not Otherwise Specified (NOS)  should  be minimized.   Invasive adenocarcinomas are classified by their predominant histological pattern.

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5.4.1 Bronchioloalveolar Carcinoma (BALC) – WHO Classification

 
In the 2004 World Health Organization (WHO) classification, the term Bronchoalveolar Carcinoma BALC is restricted to tumors in which the entire tumor shows a characteristic lepidic growth pattern (growth along the intact alveolar septa).  BALC has no features of invasion. Mucinous and non-mucinous subtypes are now on the lung cancer classification list.   In the new IASLC/ATS/ERS classification scheme, these tumors have been renamed as adenocarcinoma in situ (AIS) .

The term ‘bronchioloalveolar carcinoma’ (BALC) is becoming redundant. Hence, the lung cancers formerly classified as BALC are now known as invasive adenocarcinoma.  Furthermore, these adenocarcinomas  are classified by the stage of development from atypia to in-situ to invasive adenocarcinoma of the lung.  Invasive, non-mucinous bronchioloalveolar lesions are classified as ‘lepidic predominant’ adenocarcinoma (LPA) of the lung.  Other patterns include acinar, papillary, micropapillary, and solid predominant with mucin production.

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5.4.2 Mucinous Adenocarcinomas (non-BALC type)

 
Some invasive adenocarcinomas of the lung  show abundant mucin production. These mucinous tumors may be of low-grade or high-grade. When large amounts of mucin accumulate in the tumor cells, they produce a ‘signet ring‘ appearance.

Some mucinous adenocarcinomas produce a large amount of mucin and are associated with cyst formation.  In the past, they have had a confusing array of names, including ‘mucinous cystic tumor,’ ‘colloid carcinoma’ or ‘mucinous cystadenocarcinoma.’  They are all adenocarcinomas of the lung, and they may be high-grade or low-grade.

They are of interest in the context of lung cancer screening as they may present as a peripheral, cystic lung mass.

5.4.3 ‘Colloid’ Carcinoma

 
Colloid carcinoma of the lung is a low-grade adenocarcinoma that is associated with abundant mucin production. As this is a low-grade tumor, resection is usually curative. Interestingly, the WHO classification retains the term ‘colloid carcinoma’.  However,  it is likely that low-grade adenocarcinoma  will become the new term for this type of lung cancer.

Mucinous cystic tumors should be regarded as low-grade variants of adenocarcinoma.  A distinction from metastatic adenocarcinoma can occasionally be difficult.

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5.4.4 Papillary Adenocarcinoma

 
In the 2004 WHO classification, papillary adenocarcinomas of the lung are classified separately. Papillary adenocarcinomas of the lung have a worse prognosis than solid or alveolar adenocarcinomas.

To make the diagnosis of true papillary adenocarcinoma, secondary and tertiary branching of the papillae are present histologically.   Papillary carcinomas are divided into two groups, papillary and micropapillary, in the 2011 classification scheme.

5.4.5 Fetal Adenocarcinoma

 
Fetal adenocarcinomas  (formerly ‘endodermal tumors’) have a histological appearance that resembles fetal lung. They may be a variant of pulmonary ‘blastoma.’

The histology shows bland columnar cells that form complex glands with cells having vacuolated cytoplasm due to the presence of glycogen.  These cells do not contain mucin.

Fetal adenocarcinomas have a better prognosis than typical pulmonary adenocarcinomas.

5.4.6 Adenosquamous Carcinoma

 
Adenosquamous carcinoma of the lung consists of more than 10 % of either malignant glandular and squamous elements.  The current view is that this is a form of lung cancer that is heterogenous, and it is not a distinctive variant.

The incidence of adenosquamous lung carcinoma ranges from 0.4 to 4 % of lung cancers. Adenosquamous carcinoma is a more aggressive tumor with a poorer prognosis than either adenocarcinoma or squamous cell carcinoma.
 

Figure 5.3 Adenosquamous carcinoma of the lung.

Photomicrograph of the histology of a lung tumour shows distinctive gland
formation (a) and squamous differention (s). (H&E x40)

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References:

 
Franks TJ, Galvin JR, Jett JR, Naidich DP, Boiselle PM. Expert opinion: role of percutaneous biopsy of part-solid nodules in the IASLC/ATS/ERS international multidisciplinary classification of lung adenocarcinoma. J Thorac Imaging 2011;26(3):189. (Retrieved 10^th Feb 2015): http://www.ncbi.nlm.nih.gov/pubmed/21778873

Lee HJ, Lee CH, Jeong YJ et-al. IASLC/ATS/ERS International Multidisciplinary Classification of Lung Adenocarcinoma: novel concepts and radiologic implications. J Thorac Imaging. 2012;27 (6): 340-53. (Retrieved 10^th Feb 2015): http://www.ncbi.nlm.nih.gov/pubmed/23086014
 

More references for this section are on this page .

Patient Information:

 
American Cancer Society  What is small cell lung cancer? (Retrieved 17^th April 2015): http://www.cancer.org/cancer/lungcancer-smallcell/detailedguide/small-cell-lung-cancer-what-is-small-cell-lung-cancer

Online Tutorial   Pulmonary Adenocarcinomas: Subtyping and Differential Diagnosis. (Retrieved 17^nd April 2015): https://www.klinikum.uni-heidelberg.de/fileadmin/OnlineTutorial_PulmonaryAdenocarcinomaSubtyping/Tutorial.pdf
 

More patient information for this section is on this page .

Forward to 5C Squamous Cell, Large-Cell and Sarcomatoid Carcinoma .   Back to 5A Incidence and Classification of Lung Cancer .