A 62-year-old farmer from rural Maharashtra presents with a non-healing ulcer on the dorsum of his left hand for 8 months. The lesion started as a small nodule and gradually enlarged. On examination, there is a hyperkeratotic, indurated plaque with central ulceration and rolled edges. Regional lymph nodes are palpable. What is the investigation of choice to confirm the diagnosis?

## Investigation of Choice for Squamous Cell Carcinoma **Key Point:** Histopathological examination via tissue biopsy is the gold standard for diagnosis of squamous cell carcinoma (SCC) of skin. It provides definitive confirmation and allows assessment of differentiation grade, depth of invasion, and presence of perineural invasion. ### Why Incisional Biopsy? **High-Yield:** For suspected SCC, an incisional or excisional biopsy is mandatory because: 1. Provides tissue diagnosis with certainty 2. Allows grading (well-differentiated, moderately-differentiated, poorly-differentiated) 3. Determines depth of invasion and margins 4. Identifies high-risk features (perineural invasion, Clark level, Breslow depth equivalent) 5. Guides staging and treatment planning **Clinical Pearl:** In this case, the clinical presentation—non-healing ulcer with hyperkeratosis, induration, rolled edges, and regional lymphadenopathy—is highly suggestive of SCC, but tissue confirmation is essential before commencing definitive therapy (surgery, radiotherapy, or chemotherapy). ### Comparison of Investigations | Investigation | Role in SCC | Limitation | |---|---|---| | **Incisional/Excisional Biopsy** | Gold standard; confirms diagnosis, grades, assesses margins | Invasive; requires expertise | | **Dermoscopy** | Non-invasive screening; may show vascular patterns | Cannot confirm diagnosis; adjunctive only | | **Tzanck smear** | Used for viral infections (HSV, VZV) | Not applicable to SCC | | **Wood's lamp** | Detects pigmentation, fungal infections | No role in SCC diagnosis | **Mnemonic: BIOPSY GOLD** — **B**iopsy is **G**oldstandard, **O**btains tissue, **L**ooks at **D**epth, **S**tages **Y**our case. ### Histopathological Features of SCC The biopsy will show: - Infiltrating nests and strands of malignant squamous cells - Keratin pearl formation (well-differentiated tumors) - Increased mitotic activity - Invasion into dermis and subcutis - Possible perineural invasion (adverse prognostic sign)