Lung Cancer Pathology

Lung cancer can be divided into many subtypes, but the most important distinction is between small cell lung carcinoma (SCLC) and non–small cell lung carcinoma (NSCLC). As the names indicate, these two pathological subtypes are easily discernable by histology. In addition, the two histopathological categories are manifested through different clinical features, metastatic spread and separate modes of response to therapy.

According to the world health organization, the definition of SCLC from a histological perspective is:

A malignant epithelial tumour consisting of small cells with

scant cytoplasm, illdefined cell borders, finely granular

nuclear chromatin, and absent or inconspicuous nucleoli. The

cells are round, oval and spindle-shaped. Nuclear molding is

prominent. Necrosis is typically extensive and the mitotic

count is high.

Figure 1 shows a histological SCLC specimen:

Anything that is not SCLC is pretty much NSCLC.

Non-small cell lung cancer comprises over 85% of lung cancers and unlike SCLC is highly heterogenous in nature.

Classically, NSCLC is sub-divided into 3 major types, based on morphological grounds:

Adenocarcinoma (70% of NSCLC)

Squamous cell carcinoma (20% of NSCLC)

Large cell carcinoma (10% of NSCLC)

Figure 2 shows histological specimens from the 3 major NSCLC categories stained with hematoxylin and eosin.

In recent years and with the increasing introduction of molecular biology techniques in clinical labs, the aforementioned histological subtypes can be distinguished on the basis of molecular markers that are highly selective for one sub-type versus another. This is an important milestone, since histological sub-typing was not always possible due to the scarcity of the sample obtained (often times biopsy samples). In addition, many new NSCLC subtypes could be identified based on the presence of specific markers or mutations. For example, the presence of a mutation in the EGFR tyrosine kinase domain is almost always exclusive of squamous cell carcinoma. These findings present new paradigms in selecting patients based on molecular subtype for specific therapies, such as tyrosine kinase inhibitors.

A recent report by the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/

European Respiratory Society (ERS) Lung Adenocarcinoma

Classification has made major changes in how lung adenocarcinoma is diagnosed. The report replaces the previous classification criteria by WHO published in 2004.

The new histological classification scheme is summarized below:


1. Minimally invasive adenocarcinoma (MIA) ( 3 cm lepidic

predominant tumor with 5 mm invasion)

  • nonmucinous, mucinous, mixed mucinous/ nonmucinous

2. Invasive adenocarcinoma

  • Lepidic predominant (formerly nonmuci- nous bronchioloalveolar carcinoma (BAC) pattern, with >5 mm invasion)
  • Acinar predominant
  • Papillary predominant
  • Micropapillary predominant
  • Solid predominant with mucin

3. Variants of invasive adenocarcinoma

  • Invasive mucinous adenocarcinoma (formerly mucinous BAC)
  • Colloid
  • Fetal (low and high grade)
  • Enteric

Squamous cell carcinoma

1. Papillary

2. Clear cell

3. Small cell (probably should be discontinued)

4. Basaloid

Large cell carcinoma

1. Variants

2. Large cell neuroendocrine carcinoma (LCNEC)

  • Combined LCNEC

3. Basaloid carcinoma

4. Lymphoepithelioma-like carcinoma

5. Clear cell carcinoma

6. Large cell carcinoma with rhabdoid phenotype

Adenosquamous carcinoma

Sarcomatoid carcinomas

1. Pleomorphic carcinoma

2. Spindle cell carcinoma

3. Giant cell carcinoma

4. Carcinosarcoma

5. Pulmonary blastoma

6. Other

Carcinoid tumor

1. Typical carcinoid (TC)

2. Atypical carcinoid (AC)

Carcinomas of salivary gland type

1. Mucoepidermoid carcinoma

2. Adenoid cystic carcinoma

3. Epimyoepithelial carcinoma

Preinvasive lesions

1. Squamous dysplasia/carcinoma in situ (CIS)

2. Atypical adenomatous hyperplasia (AAH)

3. Adenocarcinoma in situ (AIS) (nonmucinous, mucinous, or

mixed nonmucinous / mucinous)

4. Diffuse idiopathic pulmonary neuroendo- crine cell

hyperplasia (DIPNECH)