Squamous Cell Carcinoma of the Skin

Ron R. Allison

BACKGROUND

Cutaneous squamous cell carcinoma (SCC) is extremely common and fortunately highly curable. As these lesions have a propensity for development and growth in visible regions of the skin, cosmetic outcomes are often very important. Critically important too is that a small subset of these cancers is locally and systemically aggressive and can become life-threatening. Therefore, optimal management for this diagnosis is of utmost concern.

This chapter reviews the state of the art in diagnosis and management of invasive cutaneous SCC with special emphasis given to those lesions at high risk for local treatment failure and also for poor cosmetic outcomes.

Nonmelanoma skin cancer is diagnosed in several million people annually, most commonly basal cell cancer followed by SCC.¹ The incidence and prevalence of SCC continues to rise due in large part to excessive unprotected sun exposure.² The intentional use of UV tanning booths further contributes to a younger population diagnosed with this malignancy. The success of immunosuppression for organ transplantation and other disease has contributed to a rise in aggressive forms of squamous cell disease.³

Classically cutaneous SCC is a disease of older individuals, with peak incidence in the sixth and seventh decade. Most lesions develop in sunlight-exposed skin, namely, the head, neck, and back of hands. Lighter color of skin (Fitzpatrick types I/II), outdoor work schedules, geographic location associated with intense sunlight, and older age increase risk of lesion development. Individuals in their 20s are more commonly being diagnosed in Australia, Florida, and
Southern California, so high levels of suspicion are always needed even in a young age group. In particular those with albinism and xeroderma pigmentosum are at extremely high risk for SCC development, even as young as 10 years of age.⁴

PRESENTATION

Although SCC is most commonly a disease of the Caucasian elderly with a history of excess sun exposure, it can afflict the young, those with pigmented skin, and particularly those with genetic and immunosuppressive states.⁵ Therefore, a high level of clinical suspicion is required.

Patients typically present with a reddish growth with a rough surface.

DIAGNOSIS

Clinical Diagnosis

SCC typically presents as a growing erythematous papule, plaque, or nodule with a keratotic surface. Diagnostic characteristics of clinical variants are described in the following text.

In most but not all cases, early forms of SCC are to be found. These actinic keratoses (AKs) are considered premalignant and by some in situ.⁶ They are somewhat irregular, raised, and erythematous. Generally, these lesions very slowly progress in size.

Actinic cheilitis (AC) is a noninvasive squamous tumor originating on sun-exposed lower lip.⁷ It may appear large and ulcerative. Of note, a substantial number of individuals with AC may have an associated invasive SCC of the lip, so caution is clinically urged.⁷

Keratoacanthoma (KA) is a rapidly growing squamous cell tumor on areas of hair follicles or the vermillion border of the lip.⁸ This lesion presents as a nodule with a central crater. It has low metastatic potential and is generally treated locally for cure.

Bowen’s disease is considered true SCC in situ. This generally presents as a distinctive well-demarcated plaque but may also appear as a flat poorly demarcated flesh-colored lesion. Erythroplasia of Queyrat is carcinoma in situ of the penis. Generally this appears reddish and velvety.

True invasive SCC may arise de novo or as progression of AK. In these cases, the majority may present as an ulcerated lesion that does not heal. Sometimes, however, true SCC can appear as small plaques or nodules. A high level of clinical suspicion is again required. In all cases, lesions may extend far beyond what is visible or palpable. In a minority of cases a solitary lymph node may be palpable.⁵ In neglected or aggressive cases, the primary may be large and associated with multiple nodal metastasis. Systemic disease is also a possibility in these cases. In particular, SCC associated with burn (Marjolin tumor) are at very high risk for nodal and regional tumor spread.⁹

Human papillomavirus (HPV)-associated SCC generally appears as an enlarging wart, growing on the penis, vulva, perianal, or periungual regions.

Clinical Workup

Lymph Node Evaluation. In addition to examination and detailed report on the primary tumor a complete skin examination should be undertaken to assess the possibility of other lesions. Tumors of the skin of the head and neck may spread to the many lymph nodes found in this anatomy.¹⁰ Therefore, careful nodal palpation should always be done. Special attention to the parotid, preauricular, postauricular, neck, and supraclavicular regions is required. Lesions of the lip should always have submental node assessment. Lesions on the arm and upper body spread to epitrochlear and axillary nodes. Lesions of the lower body and trunk should have the groin nodes highlighted during examination. A small percentage of patients are found to have clinically enlarged nodes. For these patients, radiology and biopsy procedures for the suspicious nodes are suggested as follows.¹¹

Radiologic Workup. No clear guidelines exist, but the use of ultrasound may assist in the detection of abnormal nodes. Certainly ultrasound guidance may assist in the needle biopsy of suspicious nodes.

Patients with biopsy-proven SCC and considered to have “high-risk” lesions (see later discussion) may benefit from additional radiologic workup. So too may patients with multiple suspicious nodes.

Computed tomography (CT) scans can assist in the detection of bone infiltration, disease extent, and nodal abnormalities. CT scans easily detect nodes greater than 1 cm. In select series, CT scan has changed the clinical stage for cutaneous SCC of more than 50% of patients.¹²

Magnetic resonance imaging scans are excellent for evaluating perineural invasion and for those select patients with head and neck SCC presenting with new onset of cranial nerve findings.¹³ Positron emission tomography (PET)/CT may be employed when systemic spread is felt to be at hand, particularly for extensive tumors and those that are recurrent.¹⁴

Judicious use of imaging may also assist in those patients choosing surveillance.

Staging. Unfortunately, multiple staging systems are commonly used, showing the lack of a universally accepted and validated system.¹⁵,¹⁶,¹⁷ Staging attempts to discern patients at high risk for local, regional, and systemic failure but so far has not been highly successful. In most staging systems the higher the histologic grade and larger the lesion the higher the risk for local failure. Some staging systems include tumor location as a risk factor, depth of invasion, and regional spread, among other aspects. In general, these multiple staging systems add to confusion. Currently, it may simply be more appropriate to try to define patients at high risk for failure.

High-Risk Patients. These patients may require additional or specific steps in the workup or therapy to minimize the risk of local and systemic failure, as that outcome can be life-threatening.¹⁸ In general, high-risk patients have one or multiple poor prognostic factors as follows:

Tumor >2 cm
Poorly differentiated
Invasion >6 mm
Located on ear or lip
Located on sole of foot
Arising in scar/burn
Spindle, acantholytic
Perineural invasion
Vascular invasion
Nodal invasion
Incomplete excision
Recurrent
Immunosuppressed

In particular, patients with multiple “high-risk” factors appear to develop nodal and metastatic disease at even higher rates. Select studies show only a 30% 5-year survival rate in patients with lymph node involvement.¹⁶,¹⁹ Positive margins on re-excision appears to be a strong, independent risk factor.²⁰ So too is perineural invasion, which if found on primary tumor histology offers a 35% risk of associated nodal metastasis. It should be noted that small (<0.1-mm caliber) nerve infiltration has a lower, but still definite, risk of finding metastatic disease.²¹

In particular, immunosuppression of any kind has among the highest risk factors for development of metastasis.²¹ On long-term follow-up, immunosuppressed patients may have a 10-fold increased risk for development of metastatic disease.²² These patients in particular require specialized care and frequent follow-up.²³ Risk factors are outlined in Table 13.2.1.

TABLE 13.2.1 Risk Factors for Cutaneous Squamous Cell Cancer

	Low	High
Size	<2 cm	≥2 cm
Location	Sun-exposed regions	Any recurrence Ear Lip Sole of foot Prior burn Scar Radiation sites
Depth	<6 mm Above subcutaneous fat	≥6 mm Invade subcutaneous fat
Histology	Well differentiated Verrucous	Moderately differentiated Poorly differentiated Spindle Desmoplastic Acantholytic
Perineural invasion	[circled minus]	⊕
Lymphovascular invasion	[circled minus]	⊕
Margins	[circled minus]	⊕
Immune status	Immunocompetent	Suppressed -Transplant -Disease state -Treatment related

TABLE 13.2.2 Appropriate Pathological Report for Cutaneous Squamous Cell Cancer

*Pathological report*	Name:	Date of birth:	Record #
Brief clinical description
Histology	○ Common squamous	○ Verrucous	○ Desmoplastic	○ Acantholytic
Grade	○ Well differentiated	○ Moderate	○ Poorly	○ Undifferentiated
Tumor thickness	_____mm
Margins	○ Clear	○ Involved	Pre excision photo
Lateral margins	_____mm	○ Involved
Deep margins	_____mm	○ Involved
Clark level	○ < IV	○ ≥ IV
Perineural invasion	○ Yes	○ No	Post excision photo
Lymphovascular invasion	○ Yes	○ No
Comments

Histopathology

Clearly many lesions can masquerade as SCC and SCC can masquerade as well. Therefore, histologic confirmation is a requirement before definitive treatment can be prescribed. Often needle or incisional biopsy will be diagnostic. In select small and well-demarcated tumors excisional biopsy with appropriate margin may be diagnostic and therapeutic. Potentially optical methods such as photodiagnosis may assist in diagnosis and eliminate the need for histology. However, until these methods are clinically validated, histology remains of greatest importance.²⁴

Preoperatively, a photograph with tumor measurements should be mandatory. A good description including any suspicion of spread is helpful, particularly on follow-up examination.

The vast majority of cases are confirmed on the basis of hematoxylin and eosin stains, although the use of immunohistochemical techniques, such as cytokeratins may be employed.

The final pathological report should include data that assist in prognostic classification and treatment. This must include lesion size, depth, level of dermal invasion (Clark level), status of margins, differentiation, perineural invasion, lymphatic invasion, and vascular invasion. Having this information can be critical, and the clinician should demand all this be present in the pathology report.¹¹ A model pathological report is presented in Table 13.2.2.

Squamous Cell Carcinoma

Histologic examination of well-differentiated SCC reveals aggregates of pink keratinocytes that extend and proliferate down into the dermis, with some lobules being detached from the main tumor. There is cellular atypia and nuclear pleomorphism with increased mitoses. Keratinization is seen in well-differentiated SCCs. Deeper invasion should be evaluated for perineural involvement of the tumor. Often changes consistent with AK are seen at the periphery of the tumor.²⁵ A poorly differentiated SCC may have some features of well-differentiated SCC and also more spindle-shaped tumor cells, and there is lack of keratinization.²⁵

SCC In Situ

SCC in situ/Bowen’s disease is characterized by full epidermal involvement of keratinocyte atypia, disorganization, dysmaturation, and often acanthosis. There is an increase in nuclear pleomorphism, and an increased number of mitoses is seen. Overlying parakeratosis is
observed, and the atypical keratinocytes can be seen extending into adjacent adnexa, such as hair follicles or sweat gland ducts.²⁵

Actinic Keratosis

AKs are characterized by partial-thickness (partial epidermis) keratinocyte atypia with nuclear pleomorphism. There is loss of typical epidermal maturation and overlying hyperkeratosis and parakeratosis. There is usually sparing of the hair follicle or sweat gland as it exits the epidermis. AKs may be hyperkeratotic, with significantly increased parakeratosis, or pigmented with increased basilar pigmentation.²⁵

Keratoacanthoma

KAs exhibit a classic crateriform morphology with a dome-shaped mass of well-differentiated keratinocytes with minimal atypia. There is a central hyperkeratotic core. Often there is an inflammatory infiltrate within the tumor consisting of lymphocytes, eosinophils, and neutrophil abscesses.²⁵

Only gold members can continue reading. Log In or Register to continue