A biopsy report describes an invasive squamous cell carcinoma. Malignant transformation in this lesion originates in which layer of the epithelium?

Correct answer: D. Stratum basale (basal cell layer)

• A. The stratum spinosum lies above the basal layer and contains cells that have largely ceased dividing as they differentiate upward.
• B. The stratum corneum is the outermost keratinized layer of dead, anucleate cells. It cannot initiate a neoplasm — cells there have already terminally differentiated.
• C. The stratum granulosum is a differentiating layer containing keratohyalin granules, immediately below the corneum.
• D. CORRECT. The STRATUM BASALE is the germinative layer — the only layer containing actively dividing (mitotic) stem cells. Because carcinogenesis requires the accumulation of mutations in replicating cells, dysplasia begins in the basal and parabasal layers and extends upward as it worsens. This is exactly how dysplasia is graded: mild = lower third, moderate = lower two-thirds, severe = more than two-thirds, and carcinoma in situ = full thickness. Invasion is defined by malignant cells breaching the BASEMENT MEMBRANE, which lies directly beneath the basal layer.

Note: Grading dysplasia by how far up the epithelium the atypical basal-type cells extend is high-yield. Once cells cross the basement membrane into connective tissue, the lesion is invasive carcinoma and can metastasize via lymphatics.