Page 623 - Concise Pathology for Exam Preparation ( PDFDrive )

608 SECTION II Diseases of Organ Systems

Q. Describe the clinicopathological features of squamous cell
carcinoma (SCC).

Ans. SCC may present as:
1. Crusted or scaly patches on the skin with a red, inflamed base, or
2. A growing tumour, or
3. A nonhealing ulcer.
Salient features of SCC:
• SCC generally occurs in sun-exposed areas amongst people over age 50.
• May also occur on the lips, inside the mouth, on the genitalia or anywhere on the
body.
• It is known to be associated with long-standing inflammation of the skin.
Risk factors:
• Excessive radiological exposure (X-rays)
• Exposure to arsenic and industrial carcinogens (tar and oils)
• Exposure to ultraviolet radiation (produces DNA damage)
• Chronic immunosuppression by chemotherapy or organ transplantation (reduces host
surveillance and increases susceptibility to infection by oncogenic viruses)
• Chronic nonhealing ulcers and burn scars (Marjolin ulcer)
Pathogenesis:
• Malignant transformation of normal epidermal keratinocytes is the hallmark of SCC.
The critical pathogenic event is the development of apoptotic resistance through func-
tional loss of TP53, a tumour suppressor gene.
• UV radiation causes DNA damage through the creation of pyrimidine dimers, a process
known to result in genetic mutation of TP53.
• TP53 mutations are seen in a large number of skin cancers, as well as most precursor
skin lesions, suggesting that loss of TP53 is an early event in the development
of SCC.
• Other genetic abnormalities believed to contribute to the pathogenesis of SCC include
mutations of BCL2 and RAS, alterations in intracellular signal transduction pathways
involving epidermal growth factor receptor (EGFR) and cyclooxygenase (COX) and
mutations in DNA repair genes.
Morphology:
• Squamous cell carcinoma in situ (CIS), sometimes referred to as Bowen disease, is a
precursor to invasive SCC. This lesion is characterized by nuclear atypia, frequent
mitoses, cellular pleomorphism and a disorganized progression of cells from the basal
to apical layers of the epidermis.
• Actinic keratosis (AK), a similar precancerous skin lesion, is a scaly, crusty lesion in
fair-skinned people, which occurs due to solar damage.
• Invasive SCC is differentiated from CIS and AK, based on invasion of the basement
membrane by malignant cells seen in the former. In invasive SCC nests of malignant
cells are found in the dermis, surrounded by an inflammatory infiltrate.
• Conventional SCCs can be divided into three histological grades, based on the degree
of differentiation (resemblance to normal squamous epithelium), nuclear atypia and
keratinization.
• A well-differentiated SCC (Fig. 22.1) is characterized by cells with near normal-appearing
nuclei and abundant cytoplasm with extracellular keratin pearls.
• In contrast, a poorly differentiated SCC shows a high degree of nuclear atypia with
frequent mitoses, a greater nuclear-to-cytoplasmic ratio and less keratinization.
Poorly differentiated SCCs have an increased rate of metastasis and an overall worse
prognosis.
• Moderately differentiated SCCs exhibit features between well-differentiated and
poorly differentiated lesions.
• Histological variants include acantholytic (adenoid) SCC, which is characterized by a
pseudoglandular appearance due to necrosis in the centre of tumour nests and spindle
cell SCC, which has atypical spindle-shaped cells, resembling a sarcoma. Both the vari-
ants exhibit a more aggressive clinical course.

mebooksfree.com