Squamous Cell Carcinoma

Md. Shahid Alam

Dr. Md. Shahid Alam did his masters in Ophthalmology from the prestigious Aligarh Muslim University. He completed his long term fellowship training in Orbit and oculoplastics from Sankara Nethralaya. Presently he is working as an associate consultant in the department of orbit oculoplasty reconstructive and aesthetic services, Sankara Nethralaya, Chennai. His area of interest is orbital and adnexal oncology and ocular trauma.



Bipasha Mukherjee

Dr. Bipasha Mukherjee is a fellow in Orbit & Oculoplasty from Aravind Eye Hospitals, India, and ICO fellow from University Hospital of Limoges, France, under Prof. Jean-Paul Adenis. She has undergone clinical observerships with stalwarts like Jack Rootman, Richard Collins, Geoff Rose, Mark Duffy, and Robert Goldberg.

She currently heads the department of Orbit, Oculoplasty, Aesthetic & Reconstructive services in Medical Research Foundation, Chennai. She has numerous presentations in national and international conferences and publications in peer-reviewed journals and text books. Her areas of interest include diseases of the orbit and adnexa including tumors, lacrimal surgery, socket reconstruction, traumatic lid and adnexal injuries, training residents and fellows, and photography.



Squamous cell carcinoma (SCC) is the second most common malignancy of the eyelid in Caucasians [1]. It is an invasive epithelial malignancy of keratinocytic differentiation and comprises 5–10 % of all eyelid malignancies [2]. Clinically it is liable to be misdiagnosed as basal cell carcinoma (BCC), owing to its relatively rare incidence as compared to BCC and diverse clinical presentations. Unlike BCC, it shows aggressive clinical behavior and is capable of metastasizing to lymph nodes and distant organs, causing significant morbidity and even mortality.

Incidence and Demographics

The incidence of eyelid SCC is reported to be between 0.09 and 2.42 cases per 100,000 population [3]. The highest incidence in the world is found in areas of significant ultraviolet radiation exposure, with the incidence of SCC doubling with each 10° reduction in latitude [4]. Queensland has got the highest incidence of cutaneous SCC (2,400 per 100,000) [5]. It generally affects people over 60 years of age and there is slight male preponderance [2, 6].


SCC can arise de novo from an otherwise normal skin. It can also arise from one of the following preexisting skin lesions:

  1. (a)

    Actinic keratosis: It is a partial-thickness infiltration of the epidermis by atypical keratinocytes without any violation of the basement membrane.


  2. (b)

    Intraepidermal carcinoma or SCC in situ: Intraepidermal carcinoma (IEC) or SCC in situ is a full-thickness infiltration of the epidermis by atypical keratinocytes without any violation of the basement membrane.


  3. (c)

    Bowen’s disease: It is a variant of IEC with well-defined clinical margins.


  4. (d)

    Keratoacanthoma: A variant of pseudocarcinomatous hyperplasia characterized by a well-defined elevated lesion with central keratin-filled crater. It has been classified by some authors as low-grade SCC or a precursor of SCC [7].


Risk Factors

  1. 1.

    Chronic sun exposure and acute sunburns: Chronic sun exposure is a known risk factor for the development of SCC. There is an increased incidence of SCC in the sun-exposed skin, and the incidence increases with the decrease in latitude [4]. UVB radiation (wavelength between 290 and 320 nm) induces reactive oxygen species formation and plays an important role in the formation of SCC [8].


  2. 2.

    Carcinogens: Exposure to various carcinogens like arsenic and coal tar and industrial chemicals like vinyl chloride and polycyclic aromatic hydrocarbons has been linked to the development of SCC [911].


  3. 3.

    Human papillomavirus infection [12]


  4. 4.

    Immunosuppression and organ transplant: Immunosuppression in any form is a risk factor for the development of SCC [13]. The risk of developing SCC in organ transplant recipients is 18 times higher when compared to the general population, and the tumor tends to be multiple and presents two decades earlier [14].


  5. 5.

    Intrinsic risk factors: Intrinsic risk factors for the development of SCC include albinism, preexisting chronic skin lesions, and genetic skin disorders such as xeroderma pigmentosum and epidermodysplasia verruciformis [2].


Clinical Features

SCC most commonly involves the lower lid, followed by the medial canthus, upper lid, and lateral canthus in decreasing order of frequency [3]. Usually it presents as a sessile or pedunculated plaque with telangiectasia and ulceration (Fig. 46.1a). Patients generally have other signs of skin damage in the form of actinic keratosis and chronic dermatitis [1]. SCC has got variable presentation and can be confused with other lid tumors, most commonly basal cell carcinoma [2].


Fig. 46.1
Cutaneous squamous cell carcinoma. (a) Colored photograph showing an ill-defined sessile ulcerated mass lesion involving the lateral half of the upper lid, lateral canthus, and lateral-most portion of the lower lid. Mass can be seen involving the bulbar and inferior palpebral conjunctiva (acknowledgement: Dr Saurabh Kamal, MS, FAICO and Dr Indumati Gopinathan, MD). (b) The section shows irregular tumor cells with keratin differentiation and formation of keratin pearls. Proliferation of anastomosing nests, sheets, and strands of atypical keratinocytes is also seen. They are originating in the epidermis and infiltrating into the dermis to form “eddy” or keratin pearls (black arrow) (hematoxylin and eosin stain, 20×) (Acknowledgement: Dr Saurabh Kamal, MS, FAICO and Dr Indumati Gopinathan, MD)

Presenting as Emergency

Perineural spread is a characteristic feature of SCC. An orbital invasion of SCC can involve the orbital nerves and can present with ptosis and complete ophthalmoplegia, without proptosis [1]. It can give the impression of a cavernous sinus lesion. It can also present in emergency with bleeding, infection, or ocular and adnexal myiasis [15]. Ophthalmomyiasis can lead to destruction of globe and the surrounding structures.

Tumor Spread

Locally the tumor can spread to the orbit if left neglected, making the prognosis even worse with high chances of mortality due to perineural spread into the brain.

Regional lymph nodes are the first site of metastasis, with parotid and preauricular nodes being the most commonly affected followed by submandibular, submental, and lower cervical nodes [16].

Reported rate of metastasis for SCC varies from 1 % to 21 % [17].

Histopathological Features

Histopathologically, the tumor demonstrates nests, sheets, and strands of malignant epithelial cells, showing mitotic figures that arise from the keratinocytes of stratum spinosum [4]. Keratinization is evident from the formation of keratin cysts and keratin pearls (Fig. 46.1b). Depending upon differentiation, the tumor can be graded as “well,” “moderately,” and “poorly” differentiated.


Incisional biopsy is usually done to confirm the diagnosis before planning any definite management. Taking a punch biopsy is an outpatient procedure, and the patient can then be sent home with a small dressing. It is always good to include a margin of healthy tissue for comparison. Another option is to do the biopsy under frozen section and plan for complete excision and reconstruction in the same setting. However, squamous cell carcinomas are liable to be misdiagnosed on frozen section, and it is always better to rely upon the permanent section diagnosis [18].

Magnetic resonance imaging (MRI) is frequently required in cases with suspected orbital extension. SCC has got the potential to metastasize, and occult lymph node involvement cannot be ruled out clinically. To assess lymph node involvement, lymphatic mapping with sentinel lymph node biopsy (SLNB) is being investigated [19]. At the same time, the use of SLNB for cutaneous SCC may be limited due to less metastatic spread as compared to melanoma [20]. Further study of SLNB is necessary before its implementation in the management of high-risk cutaneous SCC [21].

Positron emission tomography (PET) scan is required in cases where distant metastasis is suspected.

The American Joint Committee on Cancer (AJCC) Staging System for Eyelid Carcinoma: Seventh Edition [22]

All eyelid malignancies should be staged according to the revised AJCC staging system for eyelid carcinoma (Tables 46.1 and 46.2). It not only aids in the management but also helps in predicting the prognosis.

Table 46.1
Primary tumor definition for carcinoma of the eyelid


Primary tumor cannot be assessed


No evidence of primary tumor


Carcinoma in situ


Tumor ≤5 mm in greatest dimension; no invasion of the tarsal plate or eyelid margin


Any tumor >5 mm but <10 mm in greatest dimension; any tumor that invades the tarsal plate or eyelid margin


Any tumor >10 mm but <20 mm in greatest dimension; any tumor that invades the full thickness of the eyelid


Any tumor >20 mm in greatest dimension, any tumor that invades adjacent ocular or orbital structures, any tumor with perineural tumor invasion


Complete resection of tumor requires enucleation, exenteration, or bone resection


Tumor is not resectable because of extensive invasion of ocular, orbital, or craniofacial structures or of the brain

Table 46.2
Stage grouping for carcinoma of the eyelid






























Any T





Any N



Any T

Any N


For a better understanding, the management can be divided as follows depending upon its extent and involvement:

  1. (a)

    Tumors localized to the lid: Complete surgical excision with margin controls under frozen section is the treatment of choice for SCC primarily localized to the lids. Mohs reported a recurrence rate of 1.9 % in 161 cases of periocular SCC who underwent Mohs’ micrographic surgery [23].

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Oct 16, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Squamous Cell Carcinoma

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