Precursor Lesions of Squamous Cell Carcinoma



Precursor Lesions of Squamous Cell Carcinoma





Most anatomic pathologists are comfortable with the multihit model for the development of epithelial malignancy. As such, they are accustomed to diagnosing noninvasive premalignant neoplastic epithelial lesions at a number of sites. Perhaps the best-studied model for squamous cell carcinoma neogenesis is that for the development of squamous cell carcinoma of the uterine cervix, and most anatomic pathologists are comfortable diagnosing cervical squamous intraepithelial lesions.

There also is abundant evidence that squamous cell carcinoma of the upper aerodigestive tract develops through worsening intraepithelial neoplasia. Clinically, precursor lesions may appear white or red (or speckled) and are termed leukoplakia and erythroplakia. These clinical lesions do not correspond with definitive histologic features, although speckled and red lesions (erythroplakia) are more likely to show squamous dysplasia and be associated with concurrent squamous cell carcinoma or the eventual development of squamous cell carcinoma.1,2,3 The data regarding the risk of these lesions progressing to malignancy are varied (Table 3.1), although worsening degrees of dysplasia are associated with greater risks in most studies.3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18

Unlike in the cervix, where high-risk human papillomavirus (HPV) infection causes the majority of intraepithelial lesions, there are a myriad of causes of upper aerodigestive tract squamous intraepithelial lesions, and HPV is involved in the development of the minority of cases.19 The histologic features of most squamous intraepithelial neoplasia of the upper aerodigestive tract are thus not identical to those of the cervix, although obvious similarities exist. Undoubtedly, there is a complete spectrum of histologic changes that can be seen between the normal squamous epithelium of the upper aerodigestive tract and squamous cell carcinoma. How many lines one wishes to draw through this continuum is subjective. For the purpose of this chapter, we shall use the 2017 WHO classification systems for larynx and oral cavity (Table 3.2).20









TABLE 3.1 Risk for the Development of Squamous Cell Carcinoma of the Upper Aerodigestive Tract From Various Precursor Lesions


































































































































Study (Reference)


Location


Leukoplakia (Overall)


Dysplasia (Overall)


Mild Dysplasia


Moderate Dysplasia


Severe Dysplasia


3


Oral


45/257


8/22





4


Larynx


5/116






5


Oral


4%






6


Oral


11/248






7


Oral


7/117






8


Oral


1/117






9


Oral



9/68


1/13


3/43


5/12


10


Oral


0.13%






11


Oral



7/107





12


Oral


40/670


9/68





13


Larynx


3/92






14


Larynx


13/55


5/12





16


Oral



5/37


1/12


3/18


1/7


17


Oral


20/166


12/55


1/8


11/47


18


Oral


11/311







WHO CLASSIFICATION SCHEME

The current WHO classification schemata use two histologic parameters for the diagnosis of squamous precursor lesions of the upper aerodigestive tract: architectural and cytologic atypia (Table 3.3). As was mentioned, although there are some similarities with squamous intraepithelial neoplasia of the cervix, the two are not usually identical. Indeed, evidence suggests that intraepithelial neoplasia of the upper aerodigestive tract may appear different dependent upon its etiology.21 This is akin to squamous intraepithelial neoplasia of the vulva, where HPV-related lesions obtain a less differentiated appearance akin to lesions of the cervix, whereas other intraepithelial neoplasia may appear more differentiated (Fig. 3.1, eFig. 3.1).

Architectural disturbance is mostly considered a disturbance in cellular maturation. This is manifest histologically through lack of typical nuclear polarization, nonbasally located mitotic figures, dyskeratosis and abrupt, early keratinization. Unlike with cervical intraepithelial neoplasia, dyskeratotic cells are often very helpful for the diagnosis of squamous intraepithelial neoplasia of the upper aerodigestive tract and may be one of the few histologic clues of dysplasia. The identification of drop-shaped rete ridges can also be helpful, especially for the diagnosis of high-grade dysplastic lesions.









TABLE 3.2 WHO Classification of Precursor Lesions of Squamous Cell Carcinoma

































WHO 2005


WHO Oral Cavity 2017


WHO Larynx 2017


Histology


Hyperplasia


Mild dysplasia


Low-grade dysplasia


Thickened epithelium due to increased cell numbers. Normal maturation with no cytologic atypia.


Mild dysplasia




Lack of cellular maturation within the lower one-third of the epithelium. Cytologic atypia, generally mild and confined to the lower one-third of the epithelium.


Moderate dysplasia


Moderate dysplasia


High-grade dysplasia


Architectural disturbance in the lower two-thirds of the squamous epithelium with moderate but not severe cytologic atypia.


Severe dysplasia


Severe dysplasia



Architectural disturbance extending into the upper one-third of the epithelium with severe cytologic atypia or severe cytologic atypia with any degree of architectural abnormality.


Carcinoma in situ




Full-thickness architectural disturbance with severe cytologic atypia.

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Jan 24, 2021 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Precursor Lesions of Squamous Cell Carcinoma
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