Squamous cell carcinoma is a malignant tumor of squamous epithelium. Squamous epithelium is a tissue that lines most surfaces of the body both externally, such as the skin, and internally where it lines many organs. Squamous epithelium has a normal layered progression of cellular maturation as it grows from the basement membrane to the surface where it is eventually sloughed away. In carcinoma-affected tissue, this architecture is disturbed, and cells show aberrant features known as "atypia," which is visible under light microscopy. The extent of departure from normal squamous cells may help determine the grade of the tumor.
Cytoplasmic Features and Keratinization
Squamous epithelium surface cells are known as keratinocytes because they produce keratin. Keratin is visible as an amorphous pink material within and surrounding the cytoplasm of cells. Squamous cell carcinoma may produce excess keratin, known as "hyperkeratosis," or it may display "dyskeratosis," which is an abnormal or incomplete amount of keratinization. Histologically, this looks like excessive amounts of keratin, including "keratin pearls," which are whorled nests of keratin, and dyskeratosis, where cells often appear shrunken and deeply pink in color. Cells may also display "parakeratosis," retaining their nuclei higher up in the cell layers where normal keratinocytes would have already lost their nuclei.
Nuclear Atypia
Most aberrant features of the cell's nucleus are a direct result of excess genetic material due to the cancer's unregulated growth. Histologically, this appears as enlarged, dark or "hyperchromatic" nuclei and sometimes the appearance of one or more nucleoli. There may be a high nuclear-to-cytoplasmic ratio, known as the N:C ratio. Cells may display mitotic figures, that is nuclei in the process of division and visible as parallel stick-like figures at the center of the cell's cytoplasm. In addition to an excessive number of cells undergoing mitoses, there may be bizarre mitotic forms.
Intercellular Features
Squamous cell carcinomas sometimes lose cohesion between cells or have abnormal cell-to-cell junctions. This may be seen as "intercellular bridging," or ladder-like bridges between cells at high microscopic resolution. There could also be "acantholysis" at the surface of the epithelium, where cells are completely or partially disconnected from the underlying epithelial cells.
The cancer may cause a histologically visible immune cell response composed of variable types of inflammatory cells including neutrophils, lymphocytes, histiocytes or a mixed infiltrate.
Variant Types
In variants of squamous cell carcinoma, the cells will take on the appearance of other types of cells, including papillary cell, spindle cell, clear cell and adenoid squamous cell carcinoma, also known as pseudoglandular. Tumors may be said to be well differentiated or undifferentiated based on the extent to which they still resemble normal squamous epithelial cells. In the cases of highly undifferentiated carcinomas, special stains may need to be applied to the slides to confirm the diagnosis of squamous cell carcinoma.
References
- "Cancer Control: Journal of the Moffitt Cancer Center": Histologic Variants of Squamous Cell Carcinoma of the Skin
- Ackerman's Surgical Pathology"; Juan Rosai; 2004
- "Robbins and Cotran Pathological Basis of Disease"; Kumar; 2010
- "Primer of Dermatopathology"; Hood; 2002
