Squamous Cell Carcinoma (SCC) and Pre-Malignant Lesions

Squamous Cell Carcinoma (SCC) and Pre-Malignant Lesions

• Squamous Cell Carcinoma (SCC) is a malignant epithelial tumor characterized by a mass of atypical cells resembling normal squamous epithelium that invades underlying connective tissue. It can metastasize.
• Progression from normal epithelium to SCC involves recognizable epithelial changes like disorganization and pleomorphism (variation in cell size and shape). These changes are initially confined to the epithelium with an intact basement membrane, lacking invasion or metastatic potential. Malignant potential emerges when the lesion accesses underlying blood vessels.
• Risk of progression to SCC varies across pre-malignant lesions: Leukoplakia (~1% per year), Erythroplakia (higher risk), and Proliferative Verrucous Leukoplakia (PVL) (highest risk). However, many with potentially malignant lesions do not develop carcinoma, and observation often replaces excision.

Multistep Carcinogenesis

• Carcinogenesis is a multi-step process: Initiation (genetic alteration causing uncontrolled growth), Promotion (clonal proliferation of initiated cells), and Progression (culmination in malignant behavior).
• A key genetic model points to initial changes involving P16/CDKN2A inactivation, thereby slowing cell cycle control, leading to benign squamous hyperplasia.
• Subsequent development of dysplasia involves inactivation of FHIT and TP53 genes, creating morphological changes.
• Carcinoma in situ (severe dysplasia) results from further loss of tumor suppressor genes and increased Cyclin D1.
• Invasive carcinoma develops through further gene losses and elevated EGFR (epidermal growth factor receptor) levels, enabling metastasis.

Field Change Phenomenon

• Field change describes areas of genetically altered tissue beyond a visible lesion, highlighting that broader tissue alteration often predisposes to cancer.
• Clinically, this means excision of a visible lesion alone may overlook surrounding genetic damage.
• "Field cancerization" describes how genetically abnormal fields develop more lesions over time, leading to higher malignancy risk. This includes areas showing normal maturation in a low-risk setting (hyperkeratosis), but exhibit genetic damage, to areas showing epithelial budding into connective tissue (early invasion), reflecting a shift toward malignancy.

Oral Cancer Distribution

• The most common sites for oral cancer are the tongue (particularly lateral borders, ventral tongue, floor of mouth, lingual alveolus, retromolar regions) forming a U-shaped region that accounts for ~70% oral cancers despite representing only ~20% of the oral cavity. Saliva pooling in the lower mouth aids carcinogen retention. Hard palate and dorsum of tongue are relatively uncommon sites.

Pathology and Invasion

• Invasion, where epithelial cells enter underlying tissues, is the defining feature of carcinoma. Cells lose normal organization, becoming spindle-shaped and motile. Invasive cells are supported by fibroblasts and endothelial cells creating tumor stroma (supporting fibrous tissue). New vessel growth feeds malignant tissue needs.
• Histologically, carcinomas show large, irregular nuclei (hyperchromatism), frequent abnormal mitoses, and often loss of architectural structure. Well-differentiated carcinomas show keratin pearls and cytoplasmic keratin while poorly differentiated types are less structured, darker-staining cells with minimal keratinization. Poorly differentiated types infiltrate widely and metastasize earlier, having worse prognoses.
• Local Spread involves direct infiltration of muscle, fat, nerves, and bone. Spread can also involve perineural invasion (nerves) or vascular spread, increasing metastasis risk. Tumor growth can cause bone resorption (saucerization of cortical bone).

Metastasis

• Lymphatic metastasis is the most frequent distant spread, commonly affecting submandibular and jugulodigastric lymph nodes. Spread follows jugular chains, possibly reaching supraclavicular nodes in late stages and bilateral spread occurs if the carcinoma crosses the midline.
• Bloodstream metastasis is less common, occurring later. Common organs involved are lungs, liver, and bone. Patterns for specific sites have unique features. For example, tongue cancer invades muscle rapidly and has an unpredictable spread. Floor of mouth often spreads laterally and metastasizes more early. Alveolar ridge/gingiva typically are of lesser differentiation, spread is to bone and lower risk of lymph node metastasis. Buccal mucosa erodes soft tissue and penetrates skin and is often related to betel quid chewing. Retromolar region is difficult due to spreading to adjacent structures.

Excision for Biopsy

• Excision is critical in confirming carcinoma in a lesion, defining grade of dysplasia, identifying aneuploidy, and assuring complete removal of the highest-grade dysplasia at the lesion margins.

Management

• Early cancer detection improves survival chances.
• A multidisciplinary approach to management, using TNM staging, guides treatment decisions; aggressive approaches are often considered to aim for cure. Delayed or incomplete treatment increases recurrence and poor outcomes.
• Preoperative assessment involves imaging (to determine tumor extent and metastasis), medical evaluation (comorbidities, psychological status, dental health), and preparation for treatment. Potential complications of treatment (surgical morbidity, quality of life impact, and osteoradionecrosis) are discussed before treatment.

Summary of Genetic Changes

• Key aspects of genetic and morphological changes as cancer progresses: A concise summary of stages from Normal to Invasive Carcinoma.

Key Points

• Potentially malignant lesions rarely progress to carcinoma, yet meticulous monitoring is crucial.
• Morphological and genetic alterations shape carcinogenesis.
• Proper biopsy site selection is vital for precise diagnosis and treatment.
• Dysplasia grading and aneuploidy assessment are critical predictors of malignant potential.
• Field changes indicate genetic alterations extend beyond visible abnormalities.

Squamous Cell Carcinoma (SCC) is a malignant epithelial tumor that can metastasize. Progression to SCC involves epithelial changes like disorganization and pleomorphism, initially confined to the epithelium. Risk of progression varies across pre-malignant lesions.