CONTENTS:

4.3 Adenocarcinoma in-situ (AIS)
4.4 Squamous Dysplasia (SD) and Squamous Cell Carcinoma in-Situ (CIS)
4.4.1 Grading of Dysplasia
i. Mild dysplasia
ii. Moderate dysplasia
iii. Severe dysplasia
iv. Lung carcinoma in-situ
4.4.2 Fluorescence Bronchoscopy in Imaging Abnormal Bronchial Epithelium
4.4.3 The ‘Progression’ of Bronchial Squamous Dysplasia
4.5 Diffuse, Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH)

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4.3 Lung Adenocarcinoma in-situ (AIS)

 
There are many types of lung carcinoma in-situ.

Adenocarcinoma in situ (AIS) of lung is a newly-described entity that is pre-invasive.  AIS partly replaces non-invasive ‘bronchoalveolar carcinoma’ (BAC).  AIS is found more commonly in non-smokers, in women and individuals of Asian ethnicity.

The definition of Adenocarcinoma in-situ is a ‘localized’ mass that is less than 3 cm in diameter.   Indeed, AIS exhibits a ‘lepidic‘ pattern with atypical cells seen along the alveolar walls, but without vascular, stromal or pleural invasion.

AIS has a number of histological subtypes. The most common subtype of AIS is non-mucinous with rarely mucinous or ‘mixed’ subtypes.

Adenocarcinoma in-situ usually appears on HRCT lung imaging  as a ‘ground glass’ lung nodule or as a partly-solid lung nodule.  There is an overlap in the imaging appearances of AAH, AIS and invasive adenocarcinoma of the lung.

The prognosis of AIS is very good, with reported survival rates, following complete resection, of 100%.

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4.4 Squamous Dysplasia (SD) and Squamous Cell Lung Carcinoma in-situ (CIS)

 
Squamous Dysplasia (SD) and Squamous Cell Carcinoma in-situ (CIS) have four grades (mild, moderate, severe, and CIS).  The distribution of atypical epithelial cells and mitotic figures are important in the grading of CIS.  However, most bronchi showing SD/CIS demonstrate a range of grades.

The dysplastic changes found in the bronchial epithelium occur on the basis of squamous metaplasia.  The dysplastic changes are sequential and the frequency and number increases with the degree of atypia.  The risk of progression of SD/CIS to invasive bronchial carcinoma is unknown.  It may take between one and ten years for invasion to occur; the lesion(s) may be reversible if exposure to the carcinogen (smoking) ceases.

Figure 4.3 The Normal Bronchial Epithelium and Metaplastic Change.

Photomicrograph of the histology of the normal bronchial
epithelium (left) with ciliated surface cells. On the right is an area of
inflammation and early squamous metaplasia (X). (H&E x 40)

‘X’ marks the spot, but what is squamous metaplasia?

I don’t know but it sounds squishy!

Squamous Metaplasia refers to non-cancerous changes in the epithelial cells lining the lungs.

4.4.1 Grading of Dysplasia

 
Grading of the dysplasia of the squamous epithelium in the bronchi is similar to that in other sites, such as the cervix or esophagus.  The grades of  lung dysplasia are mild, moderate, and severe.  Lung carcinoma in-situ (CIS) indicates  severe dysplasia cases. 

An alternative method of grading the dysplasia is to refer instead to low-grade and high-grade pre-invasive dysplasia;  the latter category includes CIS. The World Health Organization (WHO) classification provides criteria for the distinction of mild, moderate, and severe dysplasia and CIS.

Mild dysplasia

 
Mild dysplasia is present when the architectural and cytological atypia is minimal. There is an expansion of the basal cell layer with cellular crowding that is confined to the lower third of the epithelium. Mitoses are absent.

ii. Moderate dysplasia

 
Moderate dysplasia shows more cytological atypia.  Maturation of epithelial cells from the base to the epithelial surface shows partial progression, but flattening of the superficial cells is still present. The basal cells now occupy two-thirds of the epithelium, and mitoses are present in the lower third.

iii. Severe dysplasiah2

 
Severe dysplasia includes cytological and architectural atypia.  Cell chromatin is coarse, and there is little cell maturation.  There may still be some superficial epithelial cell flattening.  Mitotic figures are present in the lower two-thirds of the epithelium.

iv.Lung Carcinoma in-situ (CIS)

 
Epithelial cytological atypia is severe with mitoses seen at all levels. Cell maturation is absent. A more unusual form of carcinoma in-situ exists as an exophytic, polypoid, or papillary growth. This variant of bronchial CIS can cause airway obstruction, despite the absence of mucosal invasion.

There can be considerable overlap between these four categories dysplasia and in any particular case a range of grades may be seen. These bronchial epithelial lesions do shed cytologically atypical cells into sputum, bronchial brushings and washings.

Does dysplasia mean early cell changes that may progress to cancer?

Yes, dysplasia can be an early form of pre-cancer but the cellular abnormality is restricted to the originating tissue.

To have these abnormalities detected so early has to be seen as a good thing for both monitoring and treatment.

Figure 4.4 Severe Dysplasia, Bronchial Carcinoma In-Situ.

Photomicrograph of the histology of a section of bronchus in a smoker
who developed invasive squamous carcinoma. The full thickness of
the epithelium is abnormal with enlarged, disorganized cells.
There is no invasion and the basement membrane is intact.
(H&E x 40)

4.4.2 Fluorescence Bronchoscopy in Imaging Abnormal Bronchial Epithelium

 
Fluorescence bronchoscopy techniques have been developed, such as LIFE (lung imaging fluorescence endoscopy). These techniques increase the sensitivity of bronchoscopy.  Areas of abnormal bronchial epithelium tend to show less autofluorescence than normal mucosa.  The specificity of this technique is not high; only one-third of all biopsies taken from areas that appear ‘abnormal’ during LIFE show any histological abnormality.

4.4.3 The ‘Progression’ of Bronchial Squamous Dysplasia

 
Interestingly, the progression of squamous dysplasia to Squamous Cell Carcinoma in-situ (CIS) is an area that is not well understood.  In addition,  the rate of progression to invasive squamous cell carcinoma (SCC) is also not well known. .

The earliest change in the bronchial epithelium is hyperplasia in the basal layer of cells, and this is a result of chronic irritation, usually due to smoking.  Squamous metaplasia occurs, and the earliest changes represent a response to injury.

Studies of populations screened for lung cancer using sputum cytology have shown some individuals with atypical (squamous) cells. Most of these patients will be cigarette smokers. In studies where the presence of atypical cells in the sputum has resulted in bronchoscopy, results have shown that it can take between six to 36 months for a bronchoscopically visible lesion to appear.

It is thought that early dysplastic changes may be reversible if exposure to the irritant (smoke) ceases.

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4.5 Diffuse, Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH)

 
Diffuse, idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a very rare pulmonary condition featuring a proliferation of neuroendocrine cells within the lung. In most cases, it is found in non-smokers and is asymptomatic.

Little is understood regarding the origins of pulmonary neuroendocrine tumours. There is evidence that some carcinoid tumours might be related to focal bronchial neuroendocrine cell hyperplasia. DIPNECH is a very rare lesion associated with the development of multiple carcinoid tumors.
 

Figure 4.5 A focus of Neuroendocrine Cell Hyperplasia
adjacent to a bronchiole.

Photomicrograph of the histology of a small brochiole shows
collections of bland, small dark cells that form small islands (X).
(H&E x 20)

Interestingly, women have an increased incidence of DIPNECH.  Most patients tend to be non-smokers and are asymptomatic.  DIPNECH is detected incidentally on imaging, usually for an unrelated reason. Some lesions may present with symptoms such as cough or a slowly progressive dyspnea.

The pathology shows generalized proliferation of scattered single neuroendocrine cells, forming small nodules or linear proliferations.  It may be a precursor for pulmonary carcinoid tumor.

Limited clinical studies suggest that the condition can have a variable prognosis. Treatment strategies include systemic and inhaled corticosteroids, bronchodilators, and lung resection.

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References

 
Chapman AD, Kerr KM. The association between atypical adenomatous hyperplasia and primary lung cancer. Br J Cancer 2000;83:632–6. (Retrieved 10^th Feb 2015): http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363514/pdf/83-6691317a.pdf

Auerbach O, Hammond EC, Garfinkel L. (1979). Changes in bronchial epithelium in relation to smoking. N Engl J Med 300,381–6. (Retrieved 10^th Feb 2015): http://www.ncbi.nlm.nih.gov/pubmed/759914?dopt=Abstract
 

More references for this section are on this page .

Patient Information

 
Cancer.org. Understanding Your Pathology Report. (Retrieved 10^th Feb 2015): http://www.cancer.org/treatment/understandingyourdiagnosis/understandingyourpathologyreport/lungpathology/lung-cancer-pathology

Radiopedia.Org Diffuse idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH). (Retrieved 15^th April 2015): http://radiopaedia.org/articles/diffuse-idiopathic-pulmonary-neuroendocrine-cell-hyperplasia
 

More patient information for this section is on this page.

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