Squamous Cell Carcinoma

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Disease Entity

Squamous cell carcinoma (SCC)


SCC is malignant epidermal carcinoma. SCC is the second most common eyelid malignancy, accounting less than 5% of malignant eyelid neoplasms. Basal cell carcinoma is up to 40 times more common than SCC.


SCC tends to occur at sites of sun-damaged skin, but can also arise de novo.

Risk Factors

  • Ultraviolet light exposure
  • Ionizing radiation
  • Arsenic exposure
  • Chronic irritation
  • Human papilloma virus
  • Immunocompromised status

General Pathology

Figure 1. Low-power photomicrograph of squamous cell carcinoma. A keratin pearl is prominent in the lower part of the image. (hematoxylin-eosin, original magnification x 40). Image courtesy of Marcus M. Marcet, MD FACS
Figure 2. High-power photomicrograph of squamous cell carcinoma. Keratin is seen in the center and intercellular bridges are present throughout the image. (hematoxylin-eosin, original magnification x 400). Image courtesy of Marcus M. Marcet, MD FACS

SCC is characterized by full thickness atypia of the squamous cells (Figure 1). The tumor may be graded on the amount of dedifferention. More differentiated tumors produce keratin. Nests and strands are also characteristic of well differentiated SCC. The formation of keratin decreases in less well differentiated tumors and is not seen in poorly differentiated SCC. However, characteristic intercellular bridges are generally maintained in all SCC (Figure 2).


Mutations in the p53 tumor suppressor gene commonly occur in SCC. Mutations in PTCH have also been associated with SCC.

Primary prevention

Minimize sun exposure by use of sun block products, as well as hats and appropriate clothing.


Clinical diagnosis can be suspected clinically on the basis of the appearance of the lesion. The diagnosis is confirmed by obtaining a biopsy and examining the histopathology.


Suspicious skin lesion

Physical examination

Complete eye examination, including ocular motility and assessment of proptosis

Assessment of facial sensation

Palpation of regional lymph nodes: preauricular and submandibular

Examination of the lesion includes assessment for:

  • General appearance of the lesion and periocular skin
  • Distortion of eyelid architecture or eyelid malposition
  • Presence of skin ulceration
  • Madarosis (loss of eyelashes)
  • Telangiectasias


  • Bleeding
  • Pruritis
  • Pain
  • Anesthesia

Diagnostic procedures


Differential diagnosis

The differential diagnosis includes any benign or malignant condition of the eyelid skin, including:


  • Seborrheic keratosis
  • Actinic keratosis
  • Chalazion
  • Cyst
  • Squamous papilloma
  • Blepharitis
  • Xanthelasma
  • Nevus
  • Verruca


  • Basal cell carcinoma
  • Sebaceous gland carcinoma
  • Malignant melanoma
  • Lymphoma
  • Merkel cell tumor
  • Metastasis


Surgery is the principal method of treatment. Small, well differentiated lesions may be treated with cryotherapy or photodynamic therapy.


Complete surgical excision with margin control.


Incomplete excision, metastasis, and tumor recurrence


With early, adequate treatment the prognosis is excellent. However, a mortality rate of close to 15% has been reported. Poor prognostic factors include:

  • Poorly differentiated tumors
  • Perineural spread
  • Orbital invasion
  • Immunosuppression

Additional Resources




Ophthalmic Pathology and Intraocular Tumors, Section 4. Basic and Clinical Science Course. San Francisco: American Academy of Ophthalmology; 2009.

Sehu KW, Lee WR. Ophthalmic Pathology. Oxford: Blackwell Publishing, 2005: 28, 30-32.

Srivastava M, Kelley L. Mohs' Surgery for Eyelid Malignancies. In: Albert DM, Jakobiec FA, eds. Principles and Practice of Ophthalmology, 3rd ed. Philadelphia: W.B. Saunders, 2008;3:248.

Valenzuela AA, Sullivan TJ. Squamous Cell Carcinoma in the Eyelid. In: Albert DM, Jakobiec FA, eds. Principles and Practice of Ophthalmology, 3rd ed. Philadelphia: W.B. Saunders, 2008;3:250.

Yanoff M, Sassani JW. Ocular Pathology, 6th ed. Philadelphia: Mosby Elsevier, 2009: 199-201.