Signs of Skin Malignancy
Although each tumor has characteristic clinical features, there are certain signs that are suggestive of malignancy: loss of normal lid architecture, madarosis, tethering to deeper structures, and growth or change of a lesion’s color, border, or size. It should be noted, however, that malignant tumors can have a wide variety of presentations, and a thorough knowledge of the clinical patterns, in addition to familiarity with benign eyelid lesions (see Chapter 22), is integral to determining the oculoplastic surgeon’s threshold for biopsy.
This chapter will initially discuss the generic issues of tumor staging and margin control before focusing on the more common tumors: BCC, SCC, SGC, and melanoma. A selection of the rarer tumors reported in the eyelid are briefly mentioned at the end of the chapter, although the list is by no means exhaustive.
Tumor Margin Control
Surgical excision with clear margins is the primary treatment for almost all eyelid tumors. There are two major variations in how margins are assessed.
First, the margin can be assessed intraoperatively (either with frozen sections or fast-tracked paraffin sections) or postoperatively (paraffin sections). Intraoperative margin control enables greater tissue conservation, has higher cure rates, and diminishes the need for re-excision of incompletely excised tumors.
Second, the accuracy of margin assessment is influenced by whether the specimen is sectioned in a standard breadloaf fashion, which appraises less than 1% of the tumor margin, or an attempt is made to assess 100% of the margin using either Mohs microscopic surgery (MMS) or an en face technique.4,5 In general, the latter examination techniques have superior cure rates, which are discussed in more detail in the respective sections below (Fig. 23.2).
Although BCC and SCC can be reliably assessed with frozen section techniques, tumors such as melanoma are usually examined with paraffin sections.
Staging
Staging is an assessment of the size and extent of tumor spread. The principles are the same for all cutaneous tumors, although there are tumor-specific aspects that will be discussed in the following sections on individual tumors.
Staging requires an assessment of the primary tumor (T), regional lymph nodes (N), and any distant metastases (M), that is, the TNM system. Staging can be clinical or pathologic. The clinical staging (denoted with a “c” before the stage, e.g., cT3N1M0) uses all available evidence before surgical excision, such as clinical examination and radiologic imaging. Pathologic staging (“p” before the stage) incorporates histologic examination findings.
The most widely used tumor staging system is the classification presented in the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, which is currently in its seventh edition (Table 23.1).6
Table 23.1
Eyelid Carcinoma Staging
| Primary Tumor Staging | |
| TX | Primary tumor cannot be assessed |
| T0 | No evidence of primary tumor |
| Tis | Carcinoma in situ |
| T1 | Tumor ≤5mm in greatest dimension |
| Or not invading the tarsal plate or eyelid margin | |
| T2a | Tumor >5 mm but not >10 mm in greatest dimension |
| Or any tumor that invades the tarsal plate or eyelid margin | |
| T2b | Tumor >10 mm but not >20 mm in greatest dimension |
| Or involves full thickness eyelid | |
| T3a | Tumor >20 mm in greatest dimension |
| Or any tumor that invades adjacent ocular or orbital structures | |
| Any T with perineural invasion | |
| T3b | Complete tumor resection requires enucleation, exenteration, or bone resection |
| T4 | Tumor is not resectable because of extensive invasion of ocular, orbital craniofacial structures, or brain |
| Regional Lymph Node Staging | |
| NX | Regional lymph nodes cannot be assessed |
| cN0 | No regional lymph node metastasis based on clinical evaluation or imaging |
| pN0 | No regional lymph node metastasis based on lymph node biopsy |
| N1 | Regional lymph node metastasis |
| Distant Metastasis Staging | |
| M0 | No distant metastasis |
| M1 | Distant metastasis |
Staging with the TNM system enables:
1. Comparison with other patients and those reported in the literature to provide prognosis and treatment guidelines. The current literature on eyelid malignancies provides crude data on local recurrence, regional nodal spread, distant metastases, and mortality in retrospective series of patients with differing tumor stages, frequently not treated with a consistent regime. Hence, the risks reported are of limited value in prognostication for the individual patient.
Sentinel Lymph Node Biopsy
The sentinel lymph node (SLN) is the first lymph node to which a tumor will spread. For eyelid cancers these will either be the parotid gland, the salivary gland, or the cervical nodes. The precise location is tumor and patient specific and cannot always be predicted. Moreover, there may be more than one sentinel node. Sentinel lymph node biopsy (SLNB) aims to identify subclinical, microscopic nodal spread. SLNB is not indicated if regional lymph node spread has already been identified radiologically, surgically, or with fine-needle aspiration.
The SLNB technique involves the following steps (Fig. 23.3):
1. Injection of a tracer molecule (usually technetium-labeled sulfur colloid) into the tumor. The tracer travels through the lymphatic system to local lymph nodes.
2. A handheld γ-probe is used to identify sites of tracer collection.
3. The individual or multiple nodes are excised, confirmed to contain tracer, and examined histologically.
Controversy: In principle, a negative SLNB indicates a lower risk of distant tumor spread. However, the prognostic information provided by SLNB must incorporate the risk of inaccurate selection of the SLN and the risk of tumor spread, which bypasses the SLN. These risks vary by tumor, location, and surgeon, and the benefits of SLNB for eyelid tumors have yet to be established.
Basal Cell Carcinoma
Epidemiology
Basal cell carcinoma (BCC) is the most common human malignancy, with major risk factors being ultraviolet (UV) light exposure and fair skin.7 Overall, it accounts for 80% of nonmelanoma skin cancers in whites, but the incidence varies greatly around the world. Australia has the highest rate at 884 in 100,000 per year. Despite a lower incidence in North America, the white population still has a 30% lifetime risk of BCC. In contrast, BCC is rare in dark-skinned races.
Risk Factors
▪ Ultraviolet exposure: The timing, pattern, and amount of ultraviolet (UV) radiation exposure combined with an individual’s skin type are the major risk factors for BCC. High-intensity exposure and episodes of sunburn in childhood are major determinants and intermittent lifetime exposure carries a higher risk than constant, low-level exposure.8,9 BCC is more common in men, and 95% occur in those over the age of 40 years, likely as a result of greater UV exposure.
▪ Fair complexion: Fair skin that burns without tanning, red or blonde hair, and light eye color are all independent risk factors for epidermal skin tumors.
▪ Immunosuppression: Those who have received a solid organ transplant and patients with acquired immunodeficiency syndrome (AIDS) have a markedly increased risk of BCC. Cardiac and renal transplantations confer 21 and 10 times greater risk, respectively.10 Human immunodeficiency virus (HIV) confers a twofold or threefold risk (increases inversely proportional to CD4 count).
▪ Cutaneous scars: Particularly from burns.11
▪ Ionizing radiation: Exposure to γ-rays and x-rays.
▪ Psoralen and UVA (PUVA) treatment.12
▪ Basal cell nevus syndrome (BCNS, Gorlin syndrome):
An autosomal dominant multisystem disease caused by mutation in the patched gene (prevalence of 1 in 50,000 to 160,000).13 Clinical features include multiple BCCs before age 30 years, odontogenic cysts, skeletal anomalies, and keratinizing palmar pits (Fig. 23.4).14 Ophthalmic features include eyelid epidermal cysts, periocular milia, strabismus, iris colobomas, cataract, and myelinated nerve fibers.15
▪ Albinism: A group of mainly autosomal recessive disorders with a skin melanin deficiency, with prevalence of 1 in 20,000 up to 1000 in Africa. There is an increased risk of cutaneous malignancies (predominantly SCC) from a young age.
▪ Xeroderma pigmentosum: Rare autosomal recessive disorders with defects in DNA repair, with a prevalence of 1 in 250,000 to 1 million, except in Japan (1 in 40,000).16 Patients are at increased risk of cutaneous cancers as early as the first decade.17
▪ Bazex syndrome: An autosomal dominant disorder with widened opening of hair follicles on the extremities (“ice pick” marks) and multiple facial BCCs.18
▪ Rombo syndrome: A likely autosomal dominant condition that causes inflammatory and telangiectatic skin changes.
Pathogenesis
BCCs are associated with inherited or acquired mutations in patched (PTCH) and smoothened (SMO) genes (Fig. 23.5).19 PTCH is a receptor for the sonic hedgehog (SHH) ligand. The SHH–PTCH signaling pathway plays a major role in prenatal cellular growth and differentiation and also in tumorigenesis. In the normal postnatal state, PTCH binds to and inactivates the receptor protein SMO. During embryogenesis, SHH binds to PTCH, preventing its inactivation of SMO. Mutations in PTCH or SMO may permit SMO activation. Unbound/active SMO promotes the transcription of the different genes responsible for cellular proliferation and tumor growth. In the stratified epithelium, there is epidermal hyperplasia and uncontrolled proliferation of the basal cells, leading to BCC.
For BCC to develop, two mutations causing SMO activation appear to be required. UV radiation is a common cause of acquired mutations. In BCNS, there is a germline mutation in PTCH1. A second “hit” (genetic mutation) in PTCH or SMO at any site will allow BCC development to commence. Over 90% of BCCs in patients without BCNS contain the same mutation, but these are somatic mutations, with both “hits” occurring postnatally.
Other genes and defective proteins have been implicated in BCC, such as the TP53 gene that encodes the p53 protein, cytochrome, and melanocortin-1 receptor protein, but their precise role remains to be elucidated.
Clinical Features
In whites, approximately 10% of BCC occur in the periocular area, where 43% arise on the lower eyelid, 26% at the medial canthus, 12% on the upper lid, and 8% at the lateral canthus.
The following clinical presentations can occur, with more than one of these being possible in the same lesion (Fig. 23.6):
▪ Nodular: A pearly papule or nodule with surface telangiectasia and a rolled edge. It gradually enlarges to form a dome shaped lesion, which may develop central ulceration (Fig. 23.6).
▪ Superficial: A slow-growing, scaly, erythematous patch or plaque which may resemble dermatitis (Fig. 23.7).
▪ Morpheic (sclerosing): An indurated, poorly defined, white to pink, scarlike plaque. This appearance is also sometimes termed “infiltrative” BCC (Fig. 23.8).
▪ Pigmented: BCC can have uniform or variegated brown, gray-blue, or black pigmentation (Fig. 23.9) and may mimic nevi or melanoma. This type is most common among pigmented races and is uncommon in whites.
▪ Cystic: BCC may mimic benign cysts but are usually differentiated by an associated mass or induration. Cysts are most commonly seen in the context of a nodulocystic presentation.
▪ Linear: A linear presentation is not uncommon on the eyelids and generally follows rhytids or the lid margin20,21 (Fig. 23.10).
Orbital Invasion
Orbital invasion occurs in 1.6% to 2.5% of cases (Fig. 23.11), usually in the context of neglected or recurrent multiple tumors, often located at the canthi with high-risk histopathologic features such as infiltrative subtype and perineural invasion (PNI).22 The possibility of orbital invasion must be considered in such tumors, particularly when there is fixation of the tumor to bone, extraocular movement restriction, ptosis, or globe displacement.23 However, invasion of the orbit may also be subclinical. In extremely rare cases, the tumor can gain ingress to the cranial cavity via the superior orbital fissure or directly through bone.
Metastasis
Metastatic BCC is very rare (0.002%–0.1% of cases).24,25 The risk is related to tumor size, depth, histologic subtype (infiltrating and basosquamous), and the presence of PNI.26 The median interval from presentation to metastasis is 9 years. Spread is initially to regional nodes, followed by bone, lungs, and the liver, and carries a poor prognosis.
Pathology
BCC can be histologically classified by growth pattern (morphology) or by differentiation.27,28 There are at least 20 differentiation subtypes (e.g., keratotic BCC, pigmented BCC, adenoidal, BCC with follicular or sebaceous differentiation, and infundibulocystic BCC), but these do not generally carry any clinical significance. An exception is the rare basosquamous carcinoma, which has features of both BCC and SCC with an intervening transition zone that differentiates it from a collision tumor.29 These tumors have a higher risk of recurrence and metastasis.
In contrast to differentiation, the growth pattern strongly correlates with risk of recurrence. Note that the clinical presentation will not necessarily correlate with the growth pattern.
Growth Pattern (Morphologic) Classification
Nodular BCC (50%).
Nodular BCC has variably sized nests of basaloid cells in the dermis, with peripheral palisading and retraction artifact (a clear space between tumor nodules and stroma) (Fig. 23.6E). Variants include nodulocystic BCC and micronodular BCC. Micronodular has smaller tumor nodules (≤0.15 mm) and a higher likelihood of increased subclinical extension and when infiltrative is best regarded as a variant of infiltrative BCC.30
Superficial BCC (15%).
Superficial BCCs have interconnected budding tumor nests attached to the underside of the epidermis (Fig. 23.7B).31 Because of irregular, fingerlike peripheral growth and central regression, there may be areas of apparently normal intervening epidermis in tumor sections, hence the misnomer superficial multifocal BCC. A lymphocytic inflammatory reaction between the tumor nests is typical.
Infiltrative BCC and Morpheic BCC.
Infiltrative BCCs (10%–20%) are formed of irregular groups of tumor cells with a spiky appearance (Fig. 23.8C). In the morpheic variant (5%; often classified as a distinct subtype), these irregular islands and cords of tumor cells are surrounded by dense, sclerotic stroma. All infiltrative tumors have increased risk of incomplete excision and recurrence.
Mixed BCC.
Mixed BCCs (10%–15%) contain two or more subtypes. Superficial and infiltrative patterns are often found at the lateral or deep margins. In the presence of more than one subtype, the most aggressive subtype determines the risk.
Perineural Invasion
PNI refers to tumor growth in or around a nerve (Figs. 23.15 and 23.17). It occurs by the contiguous spread of malignant cells along the potential space between a nerve and its sheath. PNI is found in 0.18% to 3% of BCC and confers a higher risk of recurrence and greater subclinical spread.32 Rarely, it may be associated with dysesthesia or pain.33
Minimum Pathologic Data Set for BCC
It is clear from the preceding discussion that infiltrative, morpheic, and micronodular growth patterns, PNI and a basosquamous subtype, denote tumors with increased risk of subclinical extension and recurrence. Hence, a pathology report should be considered incomplete unless a minimum set of data is reported (Box 23.1).
Box 23.1
Core Data Items for histopathological reporting of BCCs
Clinical
Site and type of specimen
Pathological
Microscopic
i. Infiltrative (sclerosing/infiltrating/micronodular),
b. Extradermal (tissue specified, e.g. fat, muscle, periosteum)
C. Perineural invasion: Not identified/Present/Uncertain/Cannot be assessed
D. Lymphovascular invasion: Not identified/Present/Uncertain/Cannot be assessed
F. Maximum diameter: <10mm/10-20mm/>20mm/Uncertain/Cannot be assessed
H. Pathological risk status for clinical management:
Adapted for periocular and orbital BCCs with data from Slater DN and Walsh M. Dataset for the histological reporting of primary cutaneous basal cell carcinoma. London, UK.: The Royal College of Pathologists; 2014.
Prognostic Factors
Periocular BCC is by definition within the high-risk H-zone of the face (Fig. 23.12). However, they can be further risk stratified according to tumor, site, and patient factors (Box 23.2) to determine treatment.
Investigations
BCC can mimic numerous other lid lesions. Hence, it may be clinically misdiagnosed in 10% of cases, even when assessed by a dermatologist.34 Strong consideration should be given to pretreatment biopsy to confirm the diagnosis and determine histologic subtype, which may influence treatment. An exception may be small, low-risk tumors where excisional biopsy is likely to be curative.
Management
Excision with confirmation of clear margins by histopathologic examination is the mainstay of treatment, but other options may be appropriate according to the patient’s health, wishes, and availability of resources.35
Postoperative Margin Control
The wider the surgical margin the higher the likelihood of complete clearance. Margins of 3 to 4mm are recommended for low-risk BCCs, although wider margins may be considered for high-risk tumors (Fig. 23.13).36
Surgeons must also be aware of the risk of recurrence with narrow histologic surgical margins (estimated recurrence risk of up to 15%, depending on subtype when the histologic margin is <0.5mm) or incomplete margins (recurrence in at least 30%).37 Therefore, a policy of immediate re-excision is recommended for incompletely excised tumors. Re-excision or close observation of tumors with narrow (<0.5mm) margins should be considered.38 The presence of additional risk factors such as aggressive subtype, large, or recurrent tumors should lower the threshold for re-excision.39
Intraoperative Margin Control
If available, some form of intraoperative margin control is preferable for periocular BCC to minimize recurrence risks and conserve tissue (see page 420).40 However, depending on resources, intraoperative margin control may be reserved for higher-risk tumors or used in an attempt to conserve functional structures such as the lacrimal drainage system. MMS and other en face techniques have a recurrence risk of 1% to 2% for primary eyelid tumors and 5.6% to 7.8% at 5 years for recurrent tumors. Standard bread-loaf section techniques have slightly higher rates (2%–3% 5-year recurrence rates for low-risk primary tumors).41–43
Management of Recurrent BCC
Recurrent BCC is more likely to have greater subclinical extension, irregular invasion of scar tissue, multiple foci of disease, and more aggressive histologic subtypes.44 It, therefore, has a threefold to fourfold higher risk of further recurrence compared with previously untreated lesions, regardless of the treatment modality used.45 Surgical excision of all previously treated areas, including scar tissue, preferably with intraoperative margin control, remains the first-line treatment. Adjunctive radiotherapy can be considered if there are additional risk factors, such as large size, multiple recurrences, bone involvement, PNI, aggressive histology, or metastases.
Destructive Treatment
All destructive treatments share the disadvantages of lacking histologic confirmation of clearance, higher recurrence rates than surgery, and difficulty in detection of recurrence in treated areas. With the exception of radiotherapy in advanced tumors, these modalities are not widely used in the periocular region.
Radiotherapy.
Radiotherapy is indicated in patients who are not candidates for surgery or as adjunctive treatment in high-risk lesions.46 Dosages vary between 3000 and 6000 centigrays over a 4-week to 5-week period. Short-term side effects include skin erythema, desquamation, and superficial ulceration. Longer-term effects are skin atrophy, pigmentary changes, subcutaneous fibrosis, radionecrotic ulcers, dry eye, and canalicular obstruction.
Other Destructive Methods.
Cryosurgery on the eyelids can cause hypopigmentation- or hyperpigmentation, lid notching, hypertrophic scarring, and lid margin malposition.47 A double freeze–thaw technique is generally employed (temperature −25 to −30°C). Photodynamic therapy involves the topical administration of photosensitizing agent, for example, aminolevulinic acid, and then activation of the agent with specific wavelength light to cause selective destruction. This may be considered in multiple, widespread, superficial tumors.48,49 Curettage and cautery or laser ablation are generally reserved for superficial tumors outside the periocular area.
Pharmacologic Treatment
Although surgery remains the treatment of choice for most BCCs, chemotherapy has shown promising results in patients with extensive tumors and patients with basal cell nevus syndrome.
Topical and Intralesional Therapy.
Imiquimod is a topical immune-response modifier that binds to toll-like receptor 7 and stimulates endogenous cytokine production and T-helper cell immunity.50,51 Histologic clearance can be achieved in 75% of superficial BCCs at 12 weeks, although rates are lower for other types of BCC. Imiquimod causes a vigorous local inflammatory reaction, which may be undesirable in the periocular area. Other immune response modifiers such as resiquimod are currently being tested for BCC.
Controversy: Trials of intralesional interferon have found up to 85% clearance rates. However, all patients had undergone biopsy at the time of treatment, which may have contributed to the clearance rate.52
Systemic Therapy.
Vismodegib is the most promising systemic chemotherapeutic agent currently available. It binds selectively to and inhibits SMO, thereby preventing activation of the Hh gene further down the cascade (Fig. 23.5). This stops tumor cell proliferation. Early studies report tumor shrinkage in 46% to 58% of cases and a complete response in 10% to 21%.53–55 The benefits may be higher in basal cell nevus syndrome, and there is also evidence of disease stabilization in patients with metastatic BCC. However, at present, there are only short-term follow-up studies and the risk of recurrence on stopping treatment is unknown. Moreover, vismodegib has significant side effects with up to 25% of patients stopping treatment and a small risk of mortality.
Other hedgehog pathway inhibitors such as LDE-225, IPI-926, BMS-833923, TAK-441, CUR61414, and vitamin D3 are also being assessed in human clinical trials and may be better tolerated and less likely to have resistance.56
Orbital Invasion and Metastases
If orbital invasion is suspected, computed tomography (CT) with bone windows and fat-suppressed magnetic resonance imaging (MRI) should be conducted to look for bony destruction and soft tissue changes, respectively.57 Treatment options are as follows:
▪ Local resection plus or minus adjunctive radiotherapy for patients with anterior orbital involvement alone, particularly in an only eye; if margin control is used, paraffin sections with delayed closure preferred because of difficulties with frozen sections of orbital fat
2. Radiation can be used alone in patients unfit for surgery or in an attempt to preserve the globe
3. Vismodegib can be considered as sole treatment or to reduce tumor size before surgical treatment
Lymph node dissection and adjunctive radiotherapy are indicated for nodal spread. Vismodegib and cisplatin based chemotherapy may have some efficacy for more widespread metastases.58
Prognosis
With current margin controlled techniques, primary BCC has a 5-year cure rate of 98%.59,60 Two-thirds of recurrences occur within 3 years of treatment. However, 20% occur between 5 to 10 years.61,62 Furthermore, patients are highly likely to develop further skin malignancies at other sites and may already have subclinical BCCs elsewhere on the face.63 Hence, regular skin checkups with the primary physician or dermatologist are advisable.
Patients should be counseled on prevention: sun avoidance and protection with appropriate clothing, hat, sunglasses, and high-factor sunscreen when outdoors.64
Squamous Cell Carcinoma
Epidemiology
SCC accounts for 5% to 10% of eyelid malignancies in whites but is rare in pigmented races.65,66 Although SCC shares many risk factors with BCC, including UV exposure and fair complexion, it is a more aggressive tumor with a higher risk of perineural, nodal, and distant spread.
Risk Factors
▪ UVB radiation: This is the major risk factor, and the risk is higher in fair-skinned, older people with greater sun exposure.67,68 Men have a twofold to threefold risk compared with women, probably as a result of more sun exposure.69
▪ Presence of pre-existing injured skin: Ulcers, burns, sinus tracts, vaccination scars, and chronic skin disease.
▪ Immunosuppression: Those with immunosuppression have a fivefold to 20-fold risk of developing SCC compared with the normal population. SCC is more common than BCC in patients who receive renal transplants. Similarly, patients with HIV have an increased risk of SCC.70,71
▪ Presence of precancerous lesions: For example, actinic keratosis.
▪ Genetic conditions: Albinism, xeroderma pigmentosum, epidermodysplasia verruciformis.72
▪ Other carcinogens: Ionizing radiation, PUVA, arsenic, polycyclic aromatic hydrocarbons, smoking, human papilloma virus.73,74
Pathogenesis
Chronic UVB exposure is believed to cause mutations in the DNA of keratinocytes. SCC may then develop through a multistep pathway involving proto-oncogenes and tumor suppressor genes. In 60% to 80% of cases, actinic keratosis is the initial step in the progression to invasive SCC. Actinic keratoses have an annual rate of 0.075% to 0.24% for risk of malignant transformation, although they may also regress with reduced UV exposure.75,76 Further mutations may lead directly to invasive SCC or SCC in situ. A significant proportion of SCCs and actinic keratoses contain p53 mutation, which may be the initial mutation in these tumors. Numerous other genetic alterations, which may be pathway steps or predisposing genetic instability, have been described. These include mutations of the Ras oncogene in up to 50% of SCCs and of the CDKN2A gene, which encodes the p16 tumor suppressor protein in up to 24% of SCCs.
Clinical Features
Invasive SCC
SCCs mainly develop in areas of sun exposure, particularly the head and neck. In the periocular area, they often occur at the lid margin. They are most common on the lower lid, followed by the medial canthus, the upper lid, and the lateral canthus.
SCC has a wide range of clinical appearances.69 The majority are painless, scaling nodules or plaques with irregular rolled edges (either well or ill defined), fissuring, and ulceration (Fig. 23.14). However, others can form cutaneous horns (Fig. 23.14E), papillomas, or large fungating masses.
SCC in situ (Bowen Disease, Squamous Intraepidermal Carcinoma)
In SCC in situ, the full thickness of the epidermis is replaced by atypical keratinocytes with mitotic figures at different levels. This is seen clinically as a slowly progressive, well-defined erythematous, scaly plaque (Fig. 23.15). SCC in situ has a 3% to 8% risk of malignant transformation to invasive SCC.77–79
Keratoacanthoma
Keratoacanthoma (KA) is regarded by some as a type of well-differentiated SCC with a strong propensity for spontaneous regression and by others as a distinct nonmetastasizing clinicopathologic entity (Fig. 23.16).80,81 Given that spontaneous regression of KA may cause unsightly scarring, a proportion of KA will take up to a year to regress, some tumors will recur after incomplete excision, and both clinical and pathologic differentiation of SCC and KA is difficult, it is prudent to manage these lesions as SCC with a margin controlled excision.82 It should be noted, however, that KA is much less common than SCC in the periocular area.
