More types of Lung Cancer: Neuroendocrine Carcinoma and Metastases

More Types of Lung Cancer

CONTENTS:

5.8 Neuroendocrine Carcinoma (NEC)
5.8.1 Small Cell Carcinoma
5.8.2 Non-Small Cell Neuroendocrine Tumors
5.8.3 Atypical Carcinoid Tumors
5.8.4 Large Cell Neuroendocrine Carcinoma
5.8.5 NSCLC with Neuroendocrine Differentiation
5.9 Metastases in the Lung

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5.8 Types of Lung Cancer: Neuroendocrine Tumors

Neuroendocrine tumors are now recognized to represent a spectrum from benign ‘tumorlets’ and ‘carcinoids’ to ‘small-cell carcinoma.’

Malignant neuroendocrine carcinomas of the lung include atypical carcinoid (AC) tumor, small-cell lung carcinoma (SCLC) and large-cell neuroendocrine carcinoma (LCNEC). Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNEC), a now considered to be a pre-invasive lesion (see Section 4).

Atypical carcinoids are similar to carcinoid lesions arising at other sites. Small-cell carcinomas and large-cell neuroendocrine carcinomas of the lung are characterized clinically by a more aggressive course and histologically by a much higher mitotic rate (11 or more mitoses per ten high-power fields).

The major categories of malignant neuroendocrine tumors are small-cell carcinoma (SCLC), large-cell neuroendocrine carcinoma (LCNEC), and atypical carcinoid (AC).

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5.8.1: Types of Lung Cancer: Small Cell Lung Carcinoma (SCLC)

Small cell lung carcinoma (SCLC) makes up approximately 15 % of all lung cancers. SCLC is strongly associated with cigarette smoking and is extremely rare in persons who have never smoked.

The terminology of these malignant neuroendocrine tumors has undergone some recent changes:

When lung tumors are sampled, it is clear that SCLC is often heterogeneous and can be associated with large cells. However, these tumors are as responsive to chemotherapy as are pure SCLCs.
There is no prognostic importance in the historical distinction between ‘oat cell’ and ‘intermediate cell’ subtypes.
Up to 5 % of cases of SCLC may be combined with non-small cell elements, such as squamous carcinoma or adenocarcinoma. These ‘combined‘ tumors will still respond to therapy directed to small-cell carcinoma. Tumors should consist of at least 10 % of a second component for classification as a ‘combined small cell, non-small cell carcinoma.’

Figure 5.6 Small Cell Lung Carcinoma

A. Photomicrograph of the cytology sample obtained at bronchoscopy
shows atypical nuclei, with coarse chromatin and no nucleoli and little
cytoplasm. (PAP x63). B. Photomicrograph of the histology of this tumor
shows small, dark cells with no gland or keratin formation. (H&E x40)

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5.8.2 Types of Lung Cancer: Non-Small Cell Neuroendocrine Tumors

Neuroendocrine tumors have cell characteristics that are common to them all and can help in their diagnosis microscopically. Neuroendocrine tumors all synthesize neuropeptides and contain neuroendocrine (‘dense core’) granules.

The 2004 World Health Organization (WHO) classification of lung tumors regards neuroendocrine cancer to be part of a spectrum of changes ranging from benign ‘hyperplastic’ neuroendocrine cell changes, such as carcinoid types of lung cancer ‘tumorlets’ to high-grade neuroendocrine tumors, such as small cell carcinoma and large cell neuroendocrine carcinoma.

Typical carcinoid tumor is now considered to be a low-grade neuroendocrine tumor consisting of cytologically bland cells with round or oval nuclei, finely dispersed chromatin and inconspicuous or small nucleoli. The cells are arranged in distinct trabecular, or insular growth patterns with a delicate vascular stroma, few mitoses (< 2 per ten high-powered fields) and no necrosis.

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5.8.3 Types of Lung Cancer: Atypical Carcinoid Tumors

Atypical carcinoid tumors are classified as ‘intermediate grade neuroendocrine tumors’ in the 2004 WHO classification. According to the recent diagnostic criteria, atypical carcinoids have typical morphology histologically plus one or two other features:

1) Mitoses (2 to 10 per ten high power fields)

2) Necrosis

The presence of cytological atypia is also a characteristic of atypical carcinoids but is not sufficient for a definitive types of lung cancer diagnosis. Diagnosis may be made on the basis of light microscopy alone. Immunohistochemical (IHC) staining for neuropeptides (e.g., neuron-specific enolase [NSE], chromogranin, synaptophysin) and electron microscopy may be helpful.

It is the application of IHC and electron microscopy that has revealed that some tumors with morphological appearances of NSCLC show neuroendocrine differentiation. These analyzes have shown the existence of two additional groups of tumors, the large cell neuroendocrine carcinomas and NSCLCs with neuroendocrine differentiation.

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5.8.4 Types of Lung Cancer: Large Cell Neuroendocrine Carcinoma (LCNEC)

Large cell neuroendocrine carcinoma (LCNEC) is the name given to a group of lung tumors with a neuroendocrine appearance by light microscopy, but without the morphology of carcinoid, atypical carcinoid, and small-cell carcinoma. The WHO classification system categorizes these tumors with poorly-differentiated neuroendocrine types of lung cancer carcinomas.

Histologically, LCNEC has an architecture that suggests neuroendocrine differentiation with cells arranged in trabecular or palisading patterns. Mitosis and necrosis are usually present, and neuroendocrine differentiation is usually confirmed by IHC for chromogranin or synaptophysin. These tumors are distinguished from other NSCLCs that may have immunohistochemical or electron microscopic evidence of neuroendocrine differentiation but do not appear ‘neuroendocrine’ by light microscopy.

5.8.5: Types of Lung Cancer: NSCLC with Neuroendocrine Differentiation

Between 10 % and 40 % of lung tumors diagnosed by light microscopy as NSCLC have immunophenotypic or ultrastructural evidence of neuroendocrine differentiation and are termed ‘NSCLCs with neuroendocrine differentiation.’

It is as yet unclear whether these tumors have a more aggressive course but some studies have shown either no difference in survival or improved survival when compared to similar stage NSCLCs that lack neuroendocrine differentiation. It is important to recognize neuroendocrine differentiation because these tumors respond to chemotherapy (see Section 8).

What exactly is lung cancer metastasis.

Metastatic cancer is a cancer that has spread from the place it first started to another place in the body.

So if it started in the lung, where would it go to?

The most common places for primary lung cancer to spread to are the adrenal glands, bone, brain, liver and the other lung.

5.9 Metastases to the Lung

A ‘primary‘ tumor is one that is found at its site or origin. Because cancer cells can invade into blood vessels, cancer cells can be carried to sites away from their origin and begin to grow at those sites; this is called metastasis or secondary spread.

The lung is a common site for tumor metastases. The primary tumors that commonly spread to the lungs include:

breast cancer
bladder cancer
kidney cancer
colon cancer
melanoma
pancreatic cancer
head & neck cancer
thyroid cancer
lymphoma
neuroblastoma (found in infants and children)
prostate cancer
sarcoma (from bone, muscle, or connective tissue)
Wilms’ tumor (a childhood kidney tumor)

Sometimes, cancer may spread to the lung, but the original ‘primary’ location of the cancer is not known; this is called ‘cancer of unknown primary‘ (CUP).

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References:

Battafarano RJ, Fernandez FG, Ritter J, Meyers BF, Guthrie TJ, Cooper JD, Patterson GA. (2005) Large cell neuroendocrine carcinoma: an aggressive form of non-small cell lung cancer. J Thorac Cardiovasc Surg. 2005 Jul;130(1):166-72. (Retrieved 22^ndApril 2015): http://www.ncbi.nlm.nih.gov/pubmed/15999058

Travis WD. (2014) Pathology and diagnosis of neuroendocrine tumors: lung neuroendocrine. Thorac Surg Clin.Aug;24(3):257-66. doi: 10.1016/j.thorsurg.2014.04.001 (Retrieved 22^ndApril 2015): http://www.ncbi.nlm.nih.gov/pubmed/25065926

More references for this section are on this page .

Patient Information:

American Cancer Society What are Lung Carcinoid Tumors? (Retrieved 20^th April 2015): http://www.cancer.org/cancer/lungcarcinoidtumor/detailedguide/lung-carcinoid-tumor-what-is-lung-carcinoid-tumor

MacMillan Cancer Support Neuroendocrine Tumours (NET’s) (Retrieved 22^nd April 2015): http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Neuroendocrine/Overview.aspx

More patient information for this section is on this page .

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