Squamous Cell Carcinoma

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Squamous Cell Carcinoma
Squamous Cell Carcinoma.
Squamous Cell Carcinoma. © 2019 American Academy of Ophthalmology [1]


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.

Disease Entity

International Classification of Disease (ICD)

  • ICD-9-CM 199 Squamous Cell Carcinoma (SCC)
  • ICD-10-CMC44 Squamous cell carcinoma

Disease

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. It may be classified into Cutaneous SCC (CSCC) and Mucosal SCC (MSCC) each with its own etiopathogenesis and prognosis. Ocular surface squamous neoplasia (OSSN) is beyond the scope of this write up.

Etiology

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

Risk Factors

  • Ultraviolet light exposure (CSCC): cumulative toxicity from unprotected sunlight, indoor tanning salons, esp in light pigmented individuals and ethnicities.
  • Ionizing radiation
  • Arsenic exposure
  • Chronic irritation
  • Human papilloma virus (MSCC)
  • Immunocompromised status
  • Actinic keratosis (AK)
  • Squamous intraepithelial neoplasia (Bowen's disease)
  • Xeroderma Pigmentosa

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

Pathophysiology

Mutations in the p53 tumor suppressor gene commonly occur in SCC. Mutations in PTCH have also been associated with SCC. Chronic non healings wounds and long standing burn scars may also develop malignant transformation (Marjolin's ulcer).

Primary prevention

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

Diagnosis

Diagnosis is usually made based on clinical suspicion based on the appearance of the lesion including keratinisation, especially in patients with high risk factors (see above). The diagnosis is confirmed by obtaining a biopsy and examining the histopathology.

History

Suspicious skin lesion in sun exposed skin with actinic keratosis, especially in high risk patients

Previous skin lesions, histopathology, procedures, etc

Physical examination

Complete ophthalmic examination, including ocular motility and assessment of proptosis

Assessment of entire face and sun exposed areas, facial sensation

Palpation of regional lymph nodes: preauricular, sublingual, submandibular and cervical

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

Symptoms

  • Bleeding
  • Pruritus, irritation
  • Ulceration
  • Pain
  • Anesthesia
  • Enlarging lesion
  • Crusting lesion

Diagnostic procedures

Incisional Biopsy

Differential diagnosis

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

Benign

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


Malignant

Management

Surgery is the principal method of treatment after ruling out regional spread which may be as high as 20-30%. Small, well differentiated lesions may be treated with cryotherapy or photodynamic therapy. Superficial extensive lesions may also be treated with Imiquimod.

Determination of tumor margins during surgical excision may be more difficult with SCC than with BCC, as SCC tends to have more ill-defined margins. SCC is associated with a risk of regional lymph node metastasis. For periocular SCC, the risk of regional lymph node metastasis may be as high as 20-30%, according to series from tertiary cancer centers.[22] Sentinel lymph node biopsy may be considered in high-risk patients, such as recurrent lesions or those with SCC greater than 2 cm in diameter or perineural invasion.[23] SCC is also associated with a risk of metastasis to distant organs, which increases with these high-risk features.

Surgery

Complete surgical excision with margin control is the ideal modality of management. However, determining tumor margins clinically may be challenging compared to Basal Cell Carcinoma, as the edges may be less well defined. Patients with large and extensive lesions especially with perineurial invasion and recurrent lesions may benefit from Sentinel Lymph node biopsy with radical dissection as indicated, after ruling out distant metastasis. A high degree of suspicion for orbital invasion along sensory nerves should be maintained. Exenteration may be considered in some patients with orbital involvement and with poor visual potential provided cavernous sinus is not involved. Cutaneous and orbital radiation may be considered with extensive invasion and cavernous sinus involvement.

Other modalities of management

Photodynamic therapy is emerging as a promising treatment for patients with multiple or large SCC in whom surgery is not appropriate. In such cases, PDT is associated with reasonable efficacy, good cosmesis and limited morbidity.[24] However, the precise role of PDT remains uncertain at this time.

Small and superficial lesions may also be treated with cryotherapy or Imiquimod applications

Recent advances have been made with the advent of Checkpoint inhibitors for extensive and inoperative squamous cell carcinoma and metastatic carcinoma. PD-1 inhibitors (Cemiplimab) has been recently FDA approved for this indication. EGFR inhibitors such as Cetuximab may also be helpful in some patients, although there is limited evidence till date.

Complications

Misdiagnosis, lack of histologic control, Incomplete excision, local tumor recurrence, regional spread metastasis are not uncommon with medical and medicolegal implications.

Prognosis

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

References

  1. Ophthalmic Pathology and Intraocular Tumors, Section 4. Basic and Clinical Science Course. San Francisco: American Academy of Ophthalmology; 2009.
  2. Sehu KW, Lee WR. Ophthalmic Pathology. Oxford: Blackwell Publishing, 2005: 28, 30-32.
  3. 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.
  4. 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.
  5. Yanoff M, Sassani JW. Ocular Pathology, 6th ed. Philadelphia: Mosby Elsevier, 2009: 199-201.
    1. American Academy of Ophthalmology. Squamous Cell Carcinoma. https://www.aao.org/image/squamous-cell-carcinoma-3 Accessed July 17, 2019.