CONTENT:

6.4.1 The Diagnosis of Non Small Cell Lung Cancer (NSCLC)
6.4.2 Diagnostic Histopathology Guidelines

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6.4.1 The Diagnosis of Non Small Cell Lung Cancer (NSCLC)

 
A definitive diagnosis of lung cancer is made by examining the tissue sample of the tumor.  Indeed, what type of lung cancer is present, such as Non Small Cell Lung Cancer, is an important factor in choosing further diagnostic tests.  Furthermore, other important factors for testing are the size, location and stage of the tumor.

The classification of non small cell lung cancer (NSCLC) includes adenocarcinoma and squamous cell carcinoma.  The term, ‘non small cell lung cancer’ is commonly in use in cytology and small biopsy diagnosis.  Histological sub-typing of non small cell lung cancer is done according to the World Health Organization (WHO) classification and is based on thorough histological assessment, usually of resection specimens.

There are limitations to the classification of NSCLC sub-types in small biopsy specimens.  This applies to poorly-differentiated tumors that may require extensive tissue specimen sampling to identify their nature. In small biopsy and cytology samples, studies have shown that between 40 % to 60% of NSCLC can be correctly subclassified.

Up to 5 % of lung adenocarcinomas have a small squamous component, and 15% of squamous cell carcinomas have focal glandular differentiation. This is termed tumor ‘heterogeneity,’ and it can be a confounding factor for histological classification and molecular characterization of lung tumors in small biopsies.
 

Figure 6.4 The Hematoxylin and Eosin (H&E) Stained Tissue

High power photomicrograph of the H&E appearance of a non small cell
lung cancer (NSCLC) shows the dark blue cell nuclei and the pink cell
cytoplasm. (H&E x 60)

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6.4.2   Diagnostic Histopathology Guidelines

 
For cytology samples and tissue samples, the microscopic or histological appearance of the lung cancers allows for a classification based on morphology.  The tissue morphology has prognostic significance and is a ‘biomarker’ that implies treatment and prognosis.

Sadly, some lung cancers carry a poor prognosis, even in the early-stages of the disease.  Examples of such lung cancers are ‘sarcomatoid’ and ‘basaloid’.   Furthermore,  early-stage adenocarcinomas, with a predominantly solid, micropapillary or papillary histology, carry a 70 % probability of a post-operative survival of less than two years.

Because sampling of tumor tissue for histopathology is not without risk to the patient, there are still significant numbers of patients with suspected lung cancer who never have a tissue diagnosis.  The UK guidelines recommend that  over 75 % of patients should have a tissue diagnosis before lung cancer treatment begins.

Predicting clinical outcome in lung cancer is achieved by ‘staging‘ evaluation using imaging and surgery (AJCC/UICC-TNM classification) and by histopathological grading of the primary tumor.  However,  even amongst lung cancer patients at the same stage, the outcome can vary significantly.

When a lung tumor is resected, the Pathologist may be able to characterize it using the recommended WHO classification of lung tumours (2004). However, on a small biopsy or cytology sample, using morphology alone for  non small cell lung cancer sub-typing, can be incorrect.   Thus, surgical resection specimens tend to be superior for subtyping of non small cell lung cancer.

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Controversy in Classification of Non Small Cell Lung Cancer

 
Incorrect subtyping is due to tumor heterogeneity, sampling error and a WHO classification that is applicable to whole tumor (resection) samples. In the past, if morphological evidence was insufficient to give a diagnosis of a subtype, then the breast cancer physician uses the term  ‘NSCLC not otherwise specified’ (NSCLC-NOS).

The majority of primary lung tumors are adenocarcinomas, with the proportion of adenocarcinomas increasing. A ‘non-specific’ classification is not in keeping with the demands of this new era of ‘personalized medicine‘ where targeted therapy is used in the treatment of NSCLC.

In 2011, an international classification of lung adenocarcinoma was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society and the European Respiratory Society (IASLC/ATS/ERS). This classification provides some new guidance to assist the Pathologist in reporting small biopsies and cytology specimens. In fact, in around 70% of cases, these small samples provide a diagnosis of primary lung cancer.

NSCLC is now to be classified into more specific tumor types (adenocarcinoma or squamous cell carcinoma), whenever possible. This is for the following reasons:

• Epidermal growth-factor receptor (EGFR) mutations may be present in adenocarcinoma or NSCLC-NOS, so tests are necessary.  The mutations predict response to treatment with EGFR tyrosine kinase inhibitors (TKIs).
• Adenocarcinoma histology is predictive of an improvement in outcome with pemetrexed therapy.
• For patients with a diagnosis of squamous cell who take bevacizumab (Avastin®), pulmonary hemorrhage may occur.

To classify a lung tumor further special studies, such as histochemical mucin stains and immunohistochemistry (IHC), may be necessary.  Thus, according to the most recent recommendations the term ‘NSCLC-NOS’ should be minimal, if possible.
 

Figure 6.5 The Appearance of Mitoses:

A – ‘Typical’ B & C – ‘Atypical’

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References:

Travis WD, Brambilla E, Noguchi M, et al. (2011). International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6(2), 244–285. (Retrieved 10^th Feb 2015): http://www.ncbi.nlm.nih.gov/pubmed/21252716

Rami-Porta R, Crowley JJ, Goldstraw P. (2009). The revised TNM staging system for lung cancer. Ann Thorac Cardiovasc Surg 15(1), 4–9. (Retrieved 10^th Feb 2015): http://www.atcs.jp/pdf/2009_15_1/4.pdf
 

More references for this section are on this page .

Patient Information:

Agency for Healthcare Research and Quality Diagnostic surgical pathology in lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. (Retrieved 27^th April 2015): http://www.guideline.gov/content.aspx?id=46170

International Agency for Research on Cancer (IARC) World Health Organization. WHO Histological Classification of Tumours of the Lung (Retrieved 27^th April 2015): http://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb10/bb10-chap1.pdf
 

More patient information for this section is on this page .

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