Cutaneous Squamous Cell Carcinoma (cSCC)

Clinical and Pathological Features in Depth

Pathogenesis and Risk Factors

• Chronic UV exposure: Ultraviolet light (UVB/UVA) directly damages keratinocyte DNA, leading to an accumulation of key mutations in genes such as TP53, NOTCH1 and NOTCH2, and activating the EGFR/RAS/MAPK signaling pathway.
• Precursor lesions and predisposing factors: cSCC often develops from existing precancerous lesions such as actinic keratosis (AK), actinic cheilitis (AC) or Bowen disease, or from chronic damage (old burn scars, i.e., Marjolin ulcer; non-healing chronic wounds; post-radiation fibrosis). It is also more common in people with weakened immunity (organ transplant recipients, HIV infection).

Clinical Types and Appearance

• Nodular cSCC: A firm red or flesh-colored nodule with a central keratotic plug that ulcerates and bleeds easily.
• Ulcerative cSCC: An ulcer with a raised, hard (indurated) border and a dirty, weeping or purulent base, easily mistaken for a venous or diabetic ulcer.
• Keratoacanthoma (KA): A raised, volcano-shaped tumor with a central keratin-filled crater that grows very quickly over a few weeks. Although it may partly regress on its own, it is currently classified as a well-differentiated cSCC.

Criteria for High-Risk cSCC

Under the US National Comprehensive Cancer Network (NCCN) guidelines, a cSCC is classed as high risk if it has at least one of the following features:

• Location: The H zone (central face, eyes, nose, lips, ears, scalp, anogenital area).
• Size: Larger than 2 cm on the trunk and extremities, or any size in high-risk areas (the H zone).
• Differentiation: Poorly differentiated or undifferentiated on histology.
• Depth of invasion: Tumor depth greater than 6 mm or invasion beyond the subcutaneous fat.
• Nerve or vessel invasion: Perineural invasion (PNI) or lymphovascular invasion (LVI).
• Underlying conditions: Arising in an old burn scar (Marjolin ulcer), in previously irradiated skin, or in an immunosuppressed patient.

Histopathology

• Basement membrane invasion: Nests and strands of atypical keratinocytes break through the basement membrane into the dermis and subcutis.
• Intercellular bridges and keratin pearls: In well-differentiated tumors, the cancer cells keep their intercellular bridges (spines) and form concentric keratin pearls in the center of the tumor nests.
• Histological grade (Broders grading):
  • Well differentiated (G1): More than 75% of cells clearly keratinized, with many keratin pearls.
  • Moderately differentiated (G2): 50–75% of cells keratinized.
  • Poorly differentiated (G3/G4): Fewer than 25% of cells keratinized, with marked atypia, many abnormal mitoses and few identifiable intercellular bridges.

Differential Diagnosis and Immunohistochemistry (IHC)

Our Approach to Treating Squamous Cell Carcinoma

Because cSCC can progress and spread, Haute-Derma uses a comprehensive cancer management strategy:

• Histological screening and lymph node assessment: Every cSCC patient has a careful examination of the peripheral lymph nodes (neck, armpits, groin) together with Doppler ultrasound of the regional nodes to detect micrometastases early.
• Mohs micrographic surgery and margin-controlled wide excision: We spare as much healthy tissue as possible while still achieving complete (R0) clearance.
• Treatment tailored to risk: We classify each cSCC as low or high risk to choose the right surgical margin, from 4 mm to 10 mm.
• Imaging and multidisciplinary review: For high-risk cSCC or signs of nerve or bone invasion, we arrange MRI or CT and work closely with oncology.

How We Diagnose Squamous Cell Carcinoma at Haute-Derma

To avoid missing metastatic risk and to determine the depth of invasion accurately, Haute-Derma follows a detailed four-step process:

• Clinical examination and high-resolution dermoscopy: We look for features such as yellow-white keratin, thick central scale, branching vessels, hairpin vessels or diffuse red dots.
• Deep biopsy (incisional, punch or shave): The sample must be deep enough (including deep dermis and subcutis) to assess the grade of differentiation and depth of invasion (in mm) accurately.
• Immunohistochemistry (IHC): p40, p63, EMA and BerEP4 staining in poorly differentiated or spindle cell tumors to firmly exclude melanoma or BCC.
• Regional lymph node assessment and imaging: Doppler ultrasound of the draining lymph nodes; MRI or CT when the tumor is larger than 2 cm, in a high-risk site, or suspected of perineural invasion.

How Squamous Cell Carcinoma Is Treated at Haute-Derma

cSCC treatment at Haute-Derma is individually tailored according to evidence-based standards:

• Mohs micrographic surgery (MMS):
  • The gold standard for cSCC on the face (H zone), high-risk or recurrent cSCC, and tumors with poorly defined clinical borders.
  • The entire margin is examined under the microscope during surgery, so hidden extensions of tumor can be removed completely, with disease control rates of 97–99%.
• Wide local excision (WLE):
  • Used for low-risk cSCC on the trunk and limbs.
  • Safety margins: 4 mm for low-risk cSCC; 6–10 mm for high-risk cSCC (extending down to the deep fascia).
• Assessing and managing regional lymph nodes:
  • If ultrasound or biopsy shows nodal spread, we refer you to oncology for regional lymph node dissection with adjuvant radiotherapy.
• Systemic therapy for advanced or metastatic cSCC:
  • Immunotherapy (immune checkpoint inhibitors): Anti-PD-1 drugs (cemiplimab or pembrolizumab) are the first choice for locally advanced cSCC that cannot be operated on, or for metastatic cSCC.
  • Targeted therapy: The anti-EGFR antibody cetuximab, combined with chemotherapy when indicated.
• Cosmetic reconstruction and aftercare:
  • Reconstruction with a skin flap or graft as soon as the margins are confirmed clear (R0).
  • LED therapy to reduce inflammation, prescription retinoids and a strict sun protection routine.