Squamous Precursor Lesions of the Larynx, Hypopharynx, and Trachea
Squamous dysplasia
Epidemiology and Etiology:
- Adult mostly (mean 50 y)
- M >> F
- Tobacco smoking, strong association
- Alcohol abuse, strong association
- HPV role is unsettled
Common sites:
- Supraglottic
and glottis regions most common
- Anterior true vocal cords most commonly involved
(usually not the commissure)
-
Gross features:
- Discrete or diffuse
- Leukoplakia to erythroplakia
- Patch or plaque
- Bilateral is common
Histologic features:
- Low-grade dysplasia:
- Spectrum ranging from squamous hyperplasia to
an augmentation of basal and parabasal cells
occupying as much as the lower half of the epithelium, while the upper
portion retains maturation
- Architectural criteria:
- Stratification is preserved: transition of basal
cells or augmented basal / parabasal cell
layer with perpendicular orientation to the basement membrane to
prickle cells horizontally oriented in the uppepr
part
- Spinous layer: spectrum of changes ranging
from increased spinous layer in the whole thickness up to changes in
which prickle cells are seen only in the upper epithelial half
- Basal / parabasal
layer: spectrum of changes, from 2-3 unchanged layers to augmentation
of basal and parabasal cells in thelower half of the epithelium
- Cytological criteria:
- At most minimal cellular atypia
- Parabasal cells: slightly increased cytoplasm compared to basal cells,
enlarged nuclei, uniformly distributed chromatin, no intercellular
bridges
- Rare regular mitoses in or near basal layer
- Few dyskeratoitc
cells present
- High-grade dysplasia (includes CIS in WHO 2017)
- Spectrum including immature epithelial cells
occupying at least the lower half of the epithelium and as much as the
whole epithelial thickness
- Architectural criteria:
- Abnormal maturation
- Variable degrees of disordered stratification
and polarity in as much as the whole epithelium
- Altered epithelial cells usually occupying
from half to the entire epithelial thickness
- Two subtypes: keratinizing (spinous-cell type)
and non-keratinizing (basal cell type)
- Variable degree of irregularly shaped rete
(bulbous, downwardly extending) with an intact basement membrane
- No stromal alterations
- Cytological criterial:
- Easily identified to conspicuous cellular and
nuclear atypia, including marked variation in size and shape, marked
variation in staining intensity with frequent hyperchromasia,
nucleoli increased in number and size
- Increased N:C ratio
- Increased mitoses at or above the suprabasal level, with or without atypical forms
- Dyskeratotic and apoptotic cells are frequent throughout the entire
epithelium
- Carcinoma in situ (mentioned in WHO 2017, can still
use this designation):
- Complete loss of stratification and polarity
and/or severe cytological atypia and atypical mitoses
- Notes from Thompson 2006:
- Monotonously atypical appearance
- Anisocytosis
- Anisonucleosis
- Nuclear pleomorphism
- Nuclear hyperchomasia
- Nuclear chromatin condensation
- Increased number and size of nucleoli
- Increased cellularity
- Lack of polarity
- Irregular maturation
- dyskeratosis
- Keratin pearl formation within rete
- Parakeratosis
- Increased n:c ratio
- Increased nuclear size
- Poikilocytosis
(unusual cell shapes)
- Increased mitotic figures
- Mitotic figures above basal zone
- Atypical mitoses
- Inflammatory infiltrate commonly
- No evidence of basement membrane invasion
- Glandular / duct extension maybe (not to be
interpreted as invasive)
- Morphologic changes that may suggest reactive /
regenerative / reparative proliferations:
- Ulceration, inflammation, hemorrhage,
radiation-induced mesenchymal and/or endothelial nuclear enlargement, hyperchromasia
- Stratification and maturation usually
- Absent atypical mitotic figures
- Clinical history
-
Immunophenotype:
Marker:
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Sensitivity:
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Specificity:
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Molecular features:
- Aneuploidy
- LOH / losses:
- 9p21 (earliest, most frequent) (CDKN2A gene)
- 17p13 (TP53)
- 3p26
- 3p14
- Cyclin D1 overexpression
- Telomerase activity reactivation
Other features:
- Low-grade dysplasia has 1.6 % risk of
progression to malignancy
- High-grade dysplasia has 12.5% risk of
progression to malignancy
- CIS is associated with higher risk of
progression to invasive growth (40%) and may require more extensive
surgery or radiation therapy, depending on the specific site and
contributing risk factors
- Leukoplakia appearance alone tends to be well demarcated
and lower risk of malignant transformation
- ~ 10% risk of progression to carcinoma in mild
to moderate dysplasia
- Lesions in the anterior commissure nearly always
convert to invasive SCC
- Surgery and/or radiation, dependent on the
lesion
- Hoarseness, throat irritation, sore throat,
chronic cough
- Tremendous intra- and interobserver
variability and an overall lack of reproducibility
References:
- WHO blue book (2017)
- Thompson LDR, ed. Head and Neck Pathology: A volume in the
series Foundations in Diagnostic Pathology (2006).