What is Squamous Cell Carcinoma?
Squamous cell carcinoma (SCC) is the second most common type of skin cancer
Unlike BCCs, SCCs do commonly have the ability to spread to other parts of the body. The risk of this occurring depends on its size, its location and its sub-type. It commonly presents on sun damaged skin as a pink/red lump on the skin which can be tender. Often it may have an ulcerated centre. Generally they grow faster than BCCs.
Surgical Management of Local Disease
Roy C Grekin And Paul J.M. Salmon
The surgical management of localised cutaneous squamous cell carcinoma (SCC) may be divided into the common modalities of curettage and electrodessication (C&E), tangential shave excision, standard excision and Mohs micrographic surgery (MMS). (Cryosurgery is discussed in chapter 54, and radiation therapy, in chapter 55). The choice of surgical technique must be individualized for each tumour and each patient. The approach should encompass the philosophy of total eradication of the tumour on the first occasion, because recurrent lesions carry a significantly increased risk both of local recurrence and metastasis.
Most SCCs are small and easily treated by a variety of surgical and nonsurgical methods. However, because the rate of metastasis from locally recurrent tumours arising on sun-damaged skin (excluding lip and ear) may approximate 25% (1), selection of the right treatment for each primary tumour is crucial to avoid unnecessary tragedy.
In order to make a proper choice of treatment modalities in a given setting, at least ten factors need to be taken into account. These include: underlying etiology, anatomic site, growth rate, previous treatment, diameter, depth of invasion, presence of perineural invasion, architectural pattern, degree of differentiation, and immune status of the patient (Tables 53.1 and 53.2) (2). A biopsy obtained from the deepest section of the tumour is a necessary part of this evaluation process.
Whatever therapy is planned, an adequate biopsy is as much a part of the work-up as palpation of lymph nodes or examination of the entire cutaneous surface for evidence of other malignancies. A shave biopsy that is too shallow can cause the diagnosis of invasive
SCC to be replaced with SCC in situ or the underestimation of the grade of malignancy by missing more poorly differentiated pockets of deeper cells, as well as invasion of underlying structures, such as cartilage or nerve. A deep, rolled shave biopsy, an incisional biopsy, or a punch biopsy is needed to provide the necessary information to determine appropriate therapy.
Microstaging of SCC biopsy specimens (evaluation of histologic features typically used to assess melanoma, such as Breslow depth, Clark level, and the presence or absence of tumour infiltrating lymphocytes) should be encouraged. Studies suggest that there may be prognostic value in these data (3-5). Not only does this help to plan more rational treatment, it also gathers information that, coupled with clinical data from SCC registries, may ultimately increase our ability to offer patients the most accurate advice as to appropriate treatment modalities, excision margins and prognosis.
Factors Affecting Treatment Of Choice
Many factors affect choice of treatment (Table 53.1). Location is a crucial consideration in the management of a SCC. Different anatomic sites have statistically different recurrence rates, and there are other anatomic considerations. Tumors of the lip (6-17) and ear (6, 18-24) have particularly high risk for metastasis, as do tumors in areas of scarring (25-29).
Concerns about avoiding mutilating surgery may lead to inadequate surgical margins in these areas, as well as in the areas of the central face, eyelids and digits. Finally, ablative modalities that heal by secondary intention may cause anatomic and functional distortion at free margins, such as the nasal ala, eyelid and lip.
Tumour size is also an important factor in choosing a treatment modality (1,30). Tumors larger than 2cm in diameter carry a 15.2% risk of recurrence and a 30.3% risk of metastasis, versus risks of 7.4% and 9.1% in smaller tumors, respectively. Recurrent SCCs have a higher risk of recurring again, as well as of metastasizing and are thus poorly treated by further ablative techniques (30). Growth rate also may relate to tumor aggressiveness (31). Fast-growing SCCs can be difficult to differentiate from keratoacanthomas, but the distinction is important because of the poorer prognosis association with rapidly growing SCC.
Table 53.1 Factors influencing Metastatic Rate of Tumour and Treatment Choice
- Anatomic site
- Architectural pattern
- Depth and level of invasion
- Growth rate
- Immune status of patient
- Perineural invasion
- Previous treatment
Histologic depth in SCC has not been extensively studies, but it appears to have prognostic value, as it does in melanoma (3-6). Tumours of less than 4mm in thickness, or thinner than Clark's level III, show a rate of recurrence and metastasis of 5.3% and 6.7% respectively versus 17.2% and 45.7% for deeper SCCs (30). Degree of histologic differentiation is also important; poorly differentiated tumours are twice as likely to recur and three times as likely to metastasize as well differentiated ones (4,5). Perineural invasion also carries recurrence and metastasis rates of nearly 50% when present (32-37). Histologic evidence of inflammation around an SCC appears to be a good prognostic feature 38-39).
The architectural pattern (histologic subtype) if an SCC and its expression in the physical appearance of the tumor also affects recurrence rates and prognosis, and helps in choosing one surgical modality over another. For example, desmoplastic (40) (sclerotic) SCC does not respond to curettage well, and it has poorly defined clinical margins that make excision based on visible evaluation problematic.
Finally, the immune status of the host should have a bearing on the type of treatment offered, as immuno-suppressed patients tend to have more SCCs, more poorly differentiated tumors, and higher local recurrence and metastasis rates (41-46).
Using this knowledge, the treatment of every SCC should be individualized, based on the likelihood of recurrence and metastasis.
Recurrence and Metastasis
We still do not know the definitive natural rate of recurrence and metastasis of SCC tumors (Table 53.3). The most comprehensive review of therapy for SCC of the skin (including the lip) is found in the Rowe and colleagues paper of 1992 (30). This review analysed data from 71 previous studies of local recurrence rates in SCC and 95 previous studies of local recurrence rates in SCC after treatment that included cryosurgery, C&E, radiation, surgical excision and MMS. Treatment by all surgical specialities was assessed. This study is the best analysis to date of the relationship between treatment modality and prognosis. However, it is a retrospective work, and hence its sampling may be biased toward those patients with a worse prognosis, who tend to return for follow up. Also, the majority of its data came from university-based studies where referral selection for tumors with a worse prognosis may occur. Suitable prospective studies to illuminate the true natural history of SCC are still to be done.
Table 53.2 Summary of Local Recurrence Rates of SCC of Skin, Ear and Lip by Treatment Modality and Duration of Follow-up*
|Treatment Modality||5-Year Follow-up||5-Year Follow-up (Short Term)|
|Primary Tumors of Skin|
|Curettage & Electrodesiccation (C&E)||1.3% (899)||3.7% (82)|
|Surgical excision||5.7% (1006)||8.1% (124)|
|Radiation therapy||6.7% (663)||10.0% (160)|
|Non-Mohs modalities||4.0% (3104)||7.9% (366)|
|Mohs micrographic surgery||N/A||3.1% (2065)|
|Primary Tumors of Lip|
|Non-Mohs modalities||7.6% (1046)||10.5% (7022)|
|Mohs micrographic surgery||N/A||2.3% (952)|
|Primary Tumors of Ear|
|Non-Mohs modalities||16.1% (193)||18.7% (214)|
|Mohs micrographic surgery||N/A||5.3% (337)|
|Locally Recurrent Tumors|
|Surgical excision||17.3% (52)||23.3% (34)|
|Mohs micrographic surgery||15.0% (20)||10.0% (151)|
* 5-year follow-up data used when available.
Rowe and colleagues found overall recurrence rates in primary tumors of 8.1% after surgical excision and of 3.7% and 3.1% after C&E and MMS, respectively. However, tumours treated by the two latter modalities were not comparable with each other, because the MMS lesions tended to be larger and the total number of C&E cases was small (82 C&E versus 2065 MMS). When SCCs of the lip alone were considered, MMS had a 2.3% rate of recurrence compared with 10.5% for all other modalities. Tumors of the ear were associated with an 18.7% recurrence rate with other modalities, compared with 5.3% when treated with MMS.
Table 53.3 Influence of Tumor Variables on Local Recurrence and Metastasis of SCC Expressed as Percentage of eterminate Cases. *
|Tumor Variable||Local Reoccurance % of (Determinate Cases)||Metastatis % of (Determinate Cases)|
|<2cm in diameter||7.4% (2234)||9.1% (1816)|
|>2cm in diameter||15.2% (705)||30.3% (799)|
|<4mm thick||5.3% (470)||6.7% (629)|
|>4mm thick||17.2% (227)||45.7% (339)|
|Well differentiated||13.6% (391)||9.2% (2531)|
|Poorly differentiated||28.6% (35)||
|Sun-exposed skin||7.9% (366)||5.2% (1980)|
|Ear||18.7% (214)||11.0% (991)|
|Lip||10.5% (7022)||13.7% (11,094)|
|Scar carcinoma (non-sun-exposed)||N/A||37.9% (87)|
|Previous treatment||23.3% (34)||30.3% (875)|
|Perineural involvement||47.2% (72)||47.3% (112)|
*5 year data used where available
In patients with previously treated SCCs, surgical excision resulted in a local recurrence rate of 23.3% and MMS resulted in a rate of 10.9%. Recurrence is a major determinant in treatment choice. Recurrent SCC has a significantly lower response rate to most therapeutic modalities and a markedly increased risk of metastasis. The need to prevent local recurrence is clearly demonstrated by data showing that although onl7y 5.2% of primary SCCs that develop on sun-exposed skin (excluding the lip and ear) metastasize, metastatic rates in recurrent SCCs may be as high as 25% (1). Metastatic rates for primary SCC of the ear (8.8%) and lip (13.7%) are also much lower than those for similarly located recurrent tumors (45% and 31.5%) (30). Primary tumors arising in scar tissue, chronic osteomyelitis, sinus tracts, chronic ulcers, and non-sun-exposed skin have a 37.9% risk of metastasis (30). The poor prognosis associated with these settings is difficult to explain; it may relate to different biologic features of these SCCs or simply to late diagnosis resulting from development within scar and areas of distorted anatomy.
Curettage and Electrodesiccation
This simple technique works well in superficial low-risk SCCs, including previously untreated tumors, those less than 1cm in diameter and less than 4mm (or Clark's level III) in depth, well differentiated tumors and those located in areas amenable to C&E. A representative biopsy is necessary, along with good clinical judgement, to evaluate tumor thickness before surgery. C&E should not be performed in anatomic areas where there is a high risk for recurrence, such as the nose, eyelids, lips or ears. No well controlled studies are available showing the efficacy of C&E in the treatment of SCC.
The success of curettage is highly operator-dependent (47). Variables include the sharpness of the instrument, the thoroughness of the technique, the number of cycles of C&E performed, and the width of the lateral border that is treated. The use of a 3mm to 6mm curette to debulk a tumor and then a 2mm curette to reach any pockets of subclinical extension has been advocated. Curetting should be done in all directions, followed by electrodesiccation, and then the process is repeated and typically encompasses a 4mm to 6mm lateral margin (Figure 53.1). Care should be taken to keep the electrode dry to ensure even depth of burn (48). If, in the midst of treating a tumor by C&E technique, the curette extends into the subcutis layer, excision of the site with appropriate margins should be performed.
C&E may be problematic on the lower legs of elderly people, particularly in the presence of signs of venous hypertension. These dependent sites may take many months to heal secondarily. On the anterior lower leg, excision and split thickness skin graft placement, although technically more difficult, often circumvents a slow healing tumor.
Healed C&E scars are typically hypopigmented and atrophic, but in many cases can be just as acceptable as an excision scar. However, on the dorsum of the hands, chest and shoulders, hypertrophic scars may form. The main disadvantage of C&E is the lack of a surgical specimen in which to examine margins for completeness of tumor removal or to obtain data on histologic depth of invasion. In addition, lesions which abut free margins, such as the alar rim, may cause distortion if allowed to heal by secondary intention.
In summary C&E is advocated for the treatment of low-risk, shallow SCCs up to 1cm in diameter. C&E is not a useful treatment for recurrent tumors, since failure rates are approximately 50%, and the recurrent tumors often show a more aggressive histology, poorly defined clinical margins and a greater propensity to metastasize.
Carbon Dioxide Laser Ablation
The only clear advantage of this expensive tool in the management of invasive SCC is that the level of burn to the skin can be more closely controlled than with electrocautery. Laser ablation should be considered mainly in those cases in which C&E would be used, but other specific situations exist where it may also be of benefit.
The real advantage of C02 laser surgery is in treatment of SCC in situ of the lip (49-51), vulva, and glans penis (52,53) because of the exact discoid eczema-epithelialization that can be achieved (54). In these areas, other techniques can lead to dysfunctional scarring, and C02 laser surgery is probably the treatment of choice. Finally, the C02 laser has also been used in the treatment of in situ SCC of the nail bed (55,56). However, invasive SCC of the nail bed should probably be excised with the precise margin control and tissue-sparing technique of MMS.
The disadvantages of the C02 laser, besides initial expense, are that recurrent tumor may arise from residual tumor cells located in adnexal epithelium if the burn is too superficial and, because the tumor is vaporized, no specimen is available for margin analysis.
Tangential or Shave Excision
This modality is best practiced in conjunction with curettage. After traditional curettage of a SCC, a No.15 or No.10 surgical blade is used to shave an MMS-like "disk" or "bowl" of skin completely around and under the curettage site (Figure 53.2). The site may then be cauterized, or, in an effort to improve postoperative appearance, treated with hemostatic solution only (e.g. aluminium chloride) (57). This technique is recommended for superficially invasive, low-risk SCCs only, typically located on the trunk or limbs. Care must be taken to submit a flattened pathology specimen, with marked surgical margins, and to describe the specimen clearly on the pathology request form so that margins are correctly analysed. One advantage of this technique is the creation of a tissue specimen that allows histologic examination of the margins.
Excision remains a standard mode of treatment for many forms of SCC. In many clinical settings, there are several advantages of excision over C&E. Most important is the ability to check margins for completeness of excision. Since recurrent tumors have a significant risk of metastasizing, the ability to determine tumor-free margins when treating a primary SCC should figure prominently in the decision that is made between ablative or excisional surgery. Also, the healing time is shorter and scar appearance is generally better after excision than after C&E.
Brodland and Zitelli showed that, to achieve clear surgical margins, a minimal border of 4mm of normal-appearing skin must be excised around low-risk SCCs (defined as less than 2cm in diameter, histologic grade1 and in a low-risk location), and at least a 6mm surgical margin is required around higher risk tumors (defined as histologic grade of more than 1 and more than 2cm in diameter at low-risk anatomic sites, or more than 1cm in diameter at high-risk sites) (58).
Generally if care is taken to place incisions in relaxed skin tension lines and rhytids and good technique is used, sutured wounds are cosmetically superior to those of electrosurgery or cryosurgery. Although not all SCCs curette as well as basal cell carcinoma (BCC), many physicians curette SCCs before excision, to help delineate the clinical margins of the tumor. In doing this, information on the horizontal and vertical extent can also be obtained, which may affect excision margins (Figure 53.3).
Historically, the argument for and against flap closure of high-risk SCC wounds has favored covering the wound with a skin graft to allow earlier detection of any recurrence (59). When contemplating split thickness skin grafting for this reason, one could also wonder whether or not the tumor should have been removed using MMS. If MMS is not used and flap or graft repair is required, one might consider delaying the repair until estimation of clear margins by the pathologist.
Mohs Micrographic Surgery
Because one quarter to one half of recurrent SCCs (depending on the site) metastasize, with a resulting mortality of more than 50%, the use of MMS may reduce mortality from this disease because of its higher cure rates. For this reason, MMS is becoming more often indicated in the management of SCC. Data from multiple studies clearly show that MMS is the treatment of choice for high-risk SCCs (30). The main advantage of MMS lies in its examination of 100% of the surgical margins, making incomplete excision much less likely than with standard pathologic processing (60-63). Standard intraoperative frozen section assessment reveals only about 0.1% to 0.5% of a surgical specimen's margins (64-65), which may allow small fingers of tumor to escape undetected. MMS also has the advantage of being a tissue sparing technique, because only skin involved with tumor is removed. Because of the much higher prevalence of BCC over SCC, most MMS is performed on BCC, which is reflected in discussions in the literature. However, the MMS technique is equally suited to SCC.
MMS has two distinct advantages over standard excisional or even frozen section-guided excision. These are the high cure rates and the minimization of excised normal skin, even in recurrent tumors, resulting from the specialized technique of tissue preparation. First described by Dr Frederic Mohs in 1941 (60) and modified by Tromovitch in 1970 (62), MMS is practiced by over 1000 physicians worldwide.
Patients undergo MMS most commonly in the ambulatory setting under local anesthesia (Figures 53.4 and 53.5). The tumor is often first debulked using a curette. This helps to determine more clearly the true gross margins of the tumor. A thin (1mm to 3mm thick) layer of skin is then taken around and underneath the curettage site. Incision is made at an angle of 45 degrees to the skin, rather than at 90 degrees, and this aids in the later creation of a microtome section containing a complete circumference of margin. The tissue specimen is then cut into suitably-sized pieces to fit on a microscope slide, and the edges are color-coded to allow orientation under the microscope. The orientation of these color-coded pieces is recorded on a diagram of the surgical site.
The next crucial step is the embedding of the fresh tissue as frozen blocks. The tissue is placed upside down on the cryostat platform. To prepare the blocks, the technician pushes the bevelled edges of the tissue up to the level of the anatomic undersurface of the specimen, and then freezes the manipulated tissue in place. The epidermis is now in the same plane as the deep aspect of the tissue. The block is then sliced horizontally on the microtome, producing sections that contain the entire surgical margin of that specimen. The slides are stained with hematoxylin and eosin (or toluidine blue) and examined by the surgeon. Any residual tumor can be precisely orientated to the surgical diagram, and further skin is taken only from the spot that contains tumor. The process is repeated until the tumor is completely cleared. In this way, the removal of large areas of normal skin, which can occur with standard 4mm, 6mm, or 10mm safety margins, is avoided.
MMS is thus able to conserve tissue. The fastidious examination of the complete surgical margin, rather than just a sample of the margin (as occurs with standard intraoperative frozen sections or permanent sections), enables the maximum possibility of eradicating the tumor before closure of the wound.
There are however, some difficulties with the technique particular to the management of SCC. Unlike the easily recognizable hyperchromatic cells of BCC, SCC can be difficult to discern on histologic examination of frozen sections. The polymorphous appearance of the tumor can also cause confusion. This is especially true in poorly differentiated, spindled, or highly infiltrative variants and where there is considerable lymphocytic infiltrate in the field. Having the original biopsy slides on hand, rather than just a report, may be useful. If the original biopsy is not available when commencing surgery, the surgeon can first take a biopsy for frozen section examination, before curetting the tumor. This enables identification of the particular histologic morphology of the individual tumor before looking for residual tumor in the first stage. After clearance of a clinically aggressive tumor, or a tumor with a problematic histology, some surgeons prefer to take a 2mm to 3mm margin of normal skin, because single cells of SCC (which may be unrecognizable microscopically) may be left behind. Others prefer to take an extra section in any area showing inflammation, once the wound is clear, under the premise that tiny groups of difficult-to-recognize SCC cells may be present in those areas. Finally, some authors have advocated the value of rapid cytokeratin staining to rule out residual tumor (66).
Indications in SCC
MMS should be considered 1) in any recurrent SCC, 2) where tissue-sparing is crucial, such as on the nose, eyelids, lip, genitals, or digits, 3) where the risk of recurrence is high, such as in SCC of the pinna, ear canal or lip, 4) in SCCs arising in scar, ulcer, sinus tract, osteomyelitis, or radiation poikiloderma, 5) in SCCs with high-risk histologic features such as depth of more than 4mm, poor histologic differentiation, or those showing perineural invasion or desmoplasia, 6) in SCCs with ill-defined clinical margins, 7) in verrucous carcinoma, and 8) in SCC developing in immunosuppressed hosts (Figure 53.6).
Prophylactic lymph node dissection, sentinel lymph node biopsy, and radiation therapy have been used in cases of high-risk SCC without palpable lymphadenopathy, but the literature does not yet support these approaches. (The topic of adjuvant therapy in SCC is also discussed in Chapters 59 and 60). After tumor removal, radiation therapy may be indicated in some instances. Adjuvant therapy is considered in tumors that are particularly high-risk, e.g. very large, poorly differentiated tumors; tumors showing perineural invasion; and tumors in immunosuppressed patients (30). Recurrent SCC in an area previously treated with radiation should be treated with surgery, and MMS probably is best suited to track any residual tumor through the radiation scar.
Controlled studies that address the efficacy or need for postoperative radiation therapy in stage I or II SCC are not available. Also, whether just the local tumor site, or the draining nodal basin as well, should be treated is not clear. The difficulty of predicting the site of metastatic spread in midline tumors suggests a possible role for sentinel lymph node biopsy in such cases. (For a discussion of this technique in the treatment of melanoma, see chapter 37). Alternatively, radiation therapy may be applied to the local site, and nodal basins are then treated only if there is clinical (or microscopic) evidence of metastasis. Preoperative imaging may be indicated in those patients with high-risk tumors, to facilitate any subsequent radiation treatment.
Follow-up of SCC
Because 75% of SCCs recur within the first 2 years after treatment (30), follow up examinations are recommended at intervals of 3 months for 2 years. Ninety-five percent of recurrences happen in the first 5 years after treatment; follow up should continue for 5 years. In addition, a patient presenting with an SCC is more likely to have new tumors than the general population (67-69). At follow up appointments a close examination of the surgical site and palpation of regional nodes are mandatory. Bimanual palpation of ipsilateral and contralateral submental nodes is required before and after surgery for SCC of the lip. The rest of the skin should, of course, be examined for new primaries.
The major obstacle to the appropriate treatment of this generally indolent tumor is consideration of the diagnosis. Any patient with a large wart that is recalcitrant to therapy on the genitals (Buschke-Lowenstein tumor), on the sole of the foot (epithelioma cuniculatum), or in the mouth (Ackerman tumor) should have a biopsy taken and examined by a pathologist familiar with this entity. Verrucous carcinoma is generally slow-growing, infrequently metastasizing and very treatable. Like BCC, this tumor can invade extensively, and preoperative magnet resonance imaging (MRI) is an essential part of the workup of any large and indurated verrucous carcinoma. There are reports of radiotherapy of this tumor resulting in aggressive transformation; therefore, radiotherapy should be minimized (70,71). MMS, with its capacity for margin control and tissue sparing, is the treatment of choice in verrucous carcinoma, but other modalities, such as excision, C&E, and laser excision, are among many successful therapeutic approaches. When the tumor occurs in the mouth, close examination for other SCC of the upper aerodigestive tract should be included as part of the initial and subsequent examinations (72).
Squamous Cell Carcinoma in Situ (Bowen's Disease)
By definition, SCC in situ, or Bowen's disease, if left untreated or inadequately treated, may become invasive and behave biologically as an invasive SCC (73-75). While still in situ, the disease responds well to ablative therapies, such as C&E, C02 laser ablation, or cryotherapy in which appropriate freeze-thaw times are used. However, in terminal hair-bearing areas, where involvement of the hair follicle may extend into the subcutis, these more superficial treatments may leave behind residual disease (76). Therefore, in scalp, beard, hair-bearing genital, eyebrow and eyelash regions, excision or MMS may be warranted.
Squamous Cell Carcinoma in Situ of the Lip
Because of the erythematous nature of the vermilion, the clinical margins of carcinoma in situ in this area are often indistinct, and for this reason MMS is the preferred method of excision (13). Recently, the C02 laser has been advocated as a useful tool in treatment of actinic cheilitis (49-51), because of its ability to selectively ablate the epidermis while minimally damaging the dermis.
Squamous Cell Carcinoma in Situ of the Penis
SCC in situ of the penis (erythroplasia of Queyrat, Bowen's disease of the penis) has a much higher rate of progression to invasive SCC than cancer developing on sun-exposed skin (77). In vivo toluidine blue staining may help to identify areas of subclinical involvement for biopsy. In addition to surgical excision, precise discoid eczema-epithelialization of SCC in situ may be elegantly achieved with the resurfacing C02 laser (52,53). Once invasion occurs, local metastases develop in 20% of patients, for whom the prognosis is very poor (78). Therefore, SCC in situ of the penis represents a high-risk tumor, and MMS is the treatment of choice, as it is for invasive T1 and T2 tumours, in which MMS can obviate the need for amputation (79-81). For larger tumours (progressions beyond T2), amputation may be necessary.
Squamous Cell Carcinoma of the Vulva
Prognosis in SCC of the vulva seems to be strongly related to tumor thickness. In contrast to most other cutaneous sites, a vulvar SCC more than 2mm thick represents a high-risk tumor, with a 20% chance of metastasis, which increases to 40% in tumors 4mm thick (82,83). In addition, there is a close association between vulval SCC and carcinoma of the cervix; nearly one third of patients have both. While radical and wide vulvar excision is a common treatment approach for this disease, one study has shown MMS to achieve high cure rates with much less disfigurement (84).
The differentiation of keratoacanthoma and SCC can be difficult, both clinically and histologically. In fact, some authors believe that keratoacanthoma is a variant of SCC, because some lesions thought to be keratoacanthoma grow to giant size without involution, and some keratoacanthomas have been known to metastasize (85,86). For this reason treatment of keratoacanthomas (rather than waiting for involution) is warranted. Treatment may be attempted with intralesional injections of either interferon-α-2a (87) or 5-fluorouracil. With the latter agent, a dose of 50mg is injected twice weekly for 2 weeks and weekly thereafter until resolved. If pronounced shrinkage is not seen in 2-3 weeks, definitive surgery should be considered. This may be accomplished by shaving at the base of the tumor, followed by C&E for smaller lesions in low-risk areas, or by excision with or without marginal control.
The risk of an actinic keratosis (AK) becoming an SCC seems small (88), but is significant in patients who have severe sun damage and many keratoses (89). The presence of these lesions is an important indicator of patients at risk for developing both nonmelanoma and melanoma skin cancers (90,91). Sometimes the differentiation of hyperkeratotic forms of AK and early SCC can be difficult; in such cases biopsy is indicated.
Aks, which are actinically induced, are usually easily dealt with by methods such as freezing with liquid nitrogen (92,93), chemical peeling (94-97), or application of the topical agents 5-fluorouracil (98-100) or mastoprocol (see also chapters 58 and 61). Mechanically abrasive treatments such as dermabrasion have also been promoted (101). Because keratin is a good insulator, hyperkeratotic lesions are best treated with C&E, rather than cryotherapy, unless the scale is first removed. Laser therapy may also be useful in the treatment of Aks (102). Formal excision is almost never required for these pre-malignant lesions.
In choosing appropriate treatment for a patient with SCC, consideration should be given to the many factors affecting prognosis as well as the advantages and disadvantages of the therapeutic techniques available. Each patient must be treated as an individual, and complete tumor removal must be the goal.
- Levine H. Cutaneous carcinoma of the head and neck: management of massive and previously uncontrolled lesions. Laryngoscope 1983:93:87-105.
- Kwa RE, Campana K, Moy RL. Biology of cutaneous squamous cell carcinoma. J Am Acad Dermatol 1992:26:1-26
- Breuninger H, Black B, Rassner G. Microstaging of squamous cell carcinoma. Am J Clin Pathol 1990;94:624-627.
- Friedman HI, Cooper PH, Wanebo HJ. Prognostic and therapeutic use of microstaging of cutaneous squamous cell carcinoma of the trunk and extremities. Cancer 1985;56:1009-1105.
- Immerman SC, Scanlon EF, Christ M, Knox KL. Recurrent squamous cell carcinoma of the skin. Cancer 1983;51:1537-1540.
- Robins P. Dzubow LM, Rigel DS. Squamous cell carcinoma treated by Mohs surgery: an experience with 414 cases in a period of 15 years. J Dermatol Surg Oncol 1981;7:800-801,
- Dzubow LM, Rigel DS, Robins P. Risk factors for local recurrence of primary cutaneous squamous cell carcinomas. Arch Dermatol 1982;118:900-902.
- Dinehart SM, Pollack SV. Metastasis from squamous cell carcinoma of the lower lip. Am J Otolaryngol 1992;13:363-365.
- Hosal IN, Onerci M, Kaya S, Turan E. Squamous cell carcinoma of the lower lip. Am J Otolaryngol 1992;13:363-365.
- Jorgensen K, Elbrond O, Andersen AP. Carcinoma of the lip: a series of 869 patients. Acta Otolaryngol 1973;75:312-313
- McGregor GI, Davis NL, Hay JH. Impact of cervical lymph node metastases from squamous cell carcinoma of the lip. Am J Surg 1992;163:469-471.
- McKay EN, Sellers AH. A statistical review of carcinoma of the lip. Can Med Assoc J 1964;138:333-339.
- Mehregan DA, Reonigk RK. Management of superficial squamous cell carcinoma of the lip with Mohs micrographic surgery. Cancer 1990;66:463-468.
- Mohs FE and Snow SN. Microscopically controlled surgical treatment for squamous cell carcinoma of the lower lip. Surg Gynecol Obstet 1985;160:37-41.
- Moller R, Reyman F, Hou-Jensen K. Metastases in dermatological patients with squamous cell carcinoma of the skin. Arch Dermatol 1979;115:703-705.
- Sack JG, Ford CN. Metastatic squamous cell carcinoma of the lip. Arch Otolaryngol 1978;104:282-285.
- Schreiner BF, Mattick WL. Five year end-results obtained by radiation treatment of cancer of the lip. Am J Roentgenol Rad Ther Nucl Med 1993;30:67-74.
- Afzelius LE, Gunnarsson M, Nordgren H. Guidelines for prophylactic radical lymph node dissection in cases of carcinoma of the external ear. Head Neck Surg 1980;2:361-365.
- Bart RS, Kopf AW. Squamous cell carcinoma of the ear with regional metastases. J Dermatol Surg Oncol 1976;2:289-290.
- Byers R, Kesler K, Redmon B, et al. Squamous carcinoma of the external ear. Am J Surg 1983;146:447-450.
- Lund HZ. How often does squamous cell carcinoma of the skin metastasize? Arch Dermatol 1964;92:635-637.
- Mohs F, Larson P, Iriondo M. Micrographic surgery for the microscopically controlled excision of carcinoma of the external ear. J Am Acad Dermatol 1988;19:729-737.
- Schockley WW, Stucker FJ. Squamous cell carcinoma of the external ear: a review of 75 cases. Otolaryngol Head Neck Surg 1987;97:308-312.
- Thomas SS, Matthews RN. Squamous cell carcinoma of the pinna: a six year study. Br J Plast Surg 1994;47:81-85.
- Cruikshank AH, McConnell EM, Miller DG. Malignancy in scars, chronic ulcers and sinuses. J Clin Pathol 1963;16:573-580.
- Glass RL, Spratt Js, Perez-Mesa C. Epidermoid carcinoma of lower extremities: an analysis of 35 cases. Arch Surg 1964;89;955-960.
- Kirsner RS, Garland LD. Squamous cell carcinoma arising from chronic osteomyelitis and treated by Mohs micrographic surgery. J Dermatol Surg Oncol 1994;20:141-143.
- Novick M, Gard DA, Hardy SB, et al. Burn scar carcinoma: a review and analysis of 46 cases. J Trauma 1977;17:809-817.
- Stromberg BV, Keiter JE, Wray RC, et al. Scar carcinoma: prognosis and treatment. S Med J 1977;70:821-822.
- Rowe DE, Carrol RJ, Day CONCERNING LESIONS. Prognostic factors for local recurrence, metastasis and survival rates in squamous cell carcinoma of the skin, ear and lip, implications for treatment modality selection. J Am Acad Dermatol 1992;26:467-484.
- Fitzpatrick PJ, Harwood AA. Acute epithelioma: an aggressive squamous cell carcinoma of the skin. Am J Clin Oncol 1985;8:468-471.
- Byers RM, Obrien J, Waxler J. The therapeutic and prognostic implications of nerve invasion in cancer of the lower lip. Int J Radiat Oncol Biol Pys 1978;4:215-217.
- Carter, RL, Foster CJ, Dinsdale EA, Pittam MR. Perineural spread by squamous carcinoma of the head and neck. J Clin Pathol 1983;36:1269-275.
33a. Clouston PD, Sharpe DM, Corbett AJ, et al. Perineural spread of cutaneous head and
neck cancer, its orbital and central neurological complications.
- Cottel W. Perineural invasion by squamous cell carcinoma. J Dermatol Surg Oncol 1982;8:589-600.
- Frierson HF, Cooper PH. Prognostic factors in squamous cell carcinoma of the lower lip. Hum Pathol 1986;17:346-354.
- Geopfert H, Dichtel WJ, Medina JE, et al. Perineural invasion in squamous cell carcinoma of the head and neck. Am J Surg 1984;148:542-547.
- Mendenhall WM, Parsons JT, Mendenhall NP, et al. Carcinoma of the skin of the head and neck with perineural invasion. Head Neck 1989;11:301-308.
- Crawley WA, Dellon AL, Ryan JJ. Does host response determine the prognosis in scar carcinoma? Plast Reconstr Surg 1978;62:407-414.
- Jones JH, Coyle JI. Squamous carcinoma of the inferface between neoplastic epithelium and the underlying mesenchyma. J. Dent Res 1969;48 (suppl);702-708.
- Salmon PJ, McCalmont T, Geisse J, Grekin RC. Desmoplastic squamous cell carcinoma. Arch Dermatol 1996 (in press).
- Johnson TM, Rowe DE. Nelson BR, Swanson NA. Squamous cell carcinoma of the skin (excluding lip and oral mucosa). J Am Acad Dermatol 1992;26:467-84.
- Boyle J, Briggs JD, Mackie RM, et al. Cancer, warts and sunshine in renal transplant patients: a case control study. Arch Dermatol 1986;122:1288-1293.
- Gupta AK, Cardellaa CJ, Haberman HF. Cutaneous malignant neoplasms in patients with renal transplants. Arch Dermatol 1976;122:1288-1293.
- Hardie IR, Strong WR, Hartley LCJ, et al. Skin cancer in Caucasian renal allograft patients living in a sub-tropical climate. Surgery 1980;87:177-183.
- Hoxtell EO, Mandell JJ, Murray SS. Incidence of skin cancer after renal transplantation. Arch Dermatol 1977:113:436-438.
- Mullen D, Silverberg SG, Penn I. Squamous cell carcinoma of the skin and lip in renal homograft recipients. Transplant Proc 1977;9:1129-1132.
- Kopf AW, Bart RS, Schrager D, et al. Curettage-electrodessication treatment of basal cell carcinomas. Arch Dermatol 1977;113:439-443.
- Salasche SJ. Status of curettage and electrodessication in the treatment of primary basal cell carcinoma. J Am Acad Dermatol 1983;8:496.
- Alamillos-Gandos FJ, Naval-Gias L, Dean-Ferrer A, Alonso del Hoyo JR. Carbon dioxide laser vermilionectomy for actinic cheilitis. J Oral Maxillo Surg 1993;51:118-121.
- Dufresne RG, Garrett AB, C02 laser treatment of chronic actinic cheilitis. J Am Acad Dermatol 1992;27:737-740.
- Zelickson BD, Roenigk RK. Actinic cheilitis treated with the C02 laser. Cancer 1990;65:1307-1311.
- Gerber GS. Carcinoma in situ of the penis. J Urol 1994;151:829-833.
- Greenbaum SS, Glogau RG. C02 laser treatment of erythroplasia of Queyrat. J Dermatol Surg Oncol 1989;15:747-750.
- Hobbs ER, Bailin PL, Wheeland R. Superpulsed lasers: minimising thermal damage with short duration, high irradiance pulses. J Dermatol Surg Oncol 1987;13:955-964.
- Geronemus RG. Laser surgery of the nail unit. J Dermol cream in Propylene Glycol Surg 1992;18:735-743.
- Gordon KB, Robinson J. Carbon dioxide laser vaporization for Bowen's disease of the finger. Arch Dermatol 1994;130:1250-1252.
- Brooks NA. Curettage and shave excision. J Am Acad Dermatol 1984;10:279-284.
- Brodland DG, Zitelli JA. Surgical margins for excision of primary cutaneous squamous cell carcinoma. J Am Acad Dermatol 1992;27:241-248.
- Skouge JW. Techniques for split thickness skin grafting. J Dermatol Surg Oncol 1987;13:841-849.
- Mohs FE. Chemosurgery. A microscopically controlled method of cancer excision. Arch Surg 1941;42:279-295.
- Roenigk RK. Mohs micrographic surgery. Mayo Clin Proc 1988;63:175-183.
- Tromovitch TA, Stegman SJ. Microscopically controlled excision of skin tumors: chemosurgery (Mohs) fresh tissue technique. Arch Dermatol1974;110:231-232.
- Tromovitch TA, Stegman SJ. Microscopic controlled excision of cutaneous tumors: Chemosurgery, fresh tissue technique. Cancer 1978;41:653-658.
- Davidson TM, Nahum AM, Astarita RW. Microscopic controlled excisions for epidermoid carcinoma; implications for patient follow up. J Dermatol Surg Oncol 1981;89:244-251.
- Ralpini RP. Comparison of methods for checking surgical margins. J Am Acad Dermatol 1990;23:288-294.
- Zachary CB, Rest EB, Furlong SM, et al. Rapid cytokeratin stains enhance the sensitivity of Mohs micrographic surgery for squamous cell carcinoma. J Dermatol Surg Oncol 1994;20:530-535.
- Frankel DH, Hanusa BH, Zitelli JA. New primary nonmelanoma skin cancer in patient with a history of squamous cell carcinoma of the skin. J Am Acad Dermatol 1992;26:720-6.
- Karagas MR. The risk of subsequent basal cell carcinoma and squamous cell carcinoma. JAMA 1992;267:3305-3310.
- Schreiber MM, Moon TE, Fox SH, Davidson J. The risk of developing subsequent non-melanoma skin cancer. J Am Acad Dermatol 1990;23:1114-1118.
- Owen WR, Wolfe ID, Burrett JW, et al. Epithelioma cuniculatum. S Med J 1978;71:477-479.
- Perez CA, Kraus FT, Evans JC, et al. Anaplastic transformation in verrucous carcinoma of the oral cavity after radiation therapy. Radiol 1966;86:108-115.
- Schwartz RA. Verrucous carcinoma of the skin and mucosa. J Am Acad Dermatol 1995;32:1-21.
- Mikhail GR. Cancers, precancers, and pseudocancers on the male genitalia. J Dermatol 1980;6:1027-1035.
- Sober AJ, Burstein JM. Precursors to skin cancer. Cancer 1995;75:645-650.
- Thestrup-Pedersen K, Ravnborg L, Reymann F. Morbus Bowen: a description of the disease in 617 patients. Acta Dermol cream in Propylene Glycol Venereol 1988;68:236-239.
- Hunter GA, Donald GF, Burry JN. Bowen's disease; a clinical and histological re-evaluation. Austral J Dermatol 1967;9:132-136.
- Graham JH, Helwig EB. Premalignant cutaneous and mucocutaneous diseases. In: Graham JH, Johnson WC, Helwig EB, eds. Dermal pathology. Hagerstown, MD: Harper and Row, 1972-581-597.
- Graham JH, Helwig EB. Erythroplasia of Queyrat. A clinicopatholgic and histochemical study. Cancer 1973;32:1396-1399.
- Brown MD, Zachary CB, Grekin RC, Swanson NA. Genital tumors: their management by micrographic surgery. J Am Acad Dermatol 1992;26:576-578.
- Horenblas S, van Tinteren H, Delemarre JFM, et al. Squamous cell carcinoma of the penis. 2. Treatment of the primary tumour. J Urol 1992;147:1533-1538.
- Mohs FE, Snow SN, Messing, Kuglitsch ME. Microscopically controlled surgery in the treatment of carcinoma of the penis. J Urol 1985;133:961-966.
- Noumoff JS, Farber M. Tumors of the vulva. Int J Dermatol 1986;26:552-563.
- Binder SW, Huang I, Follow up YS, et al. Risk factors for the development of lymph node metastasis in vulvar squamous cell carcinoma. Gynecol Oncol 1990;37:9-16.
- Brown MD, Zachary CB, Grekin RC, Swanson NA. Genital tumors; their management by micrographic surgery. J Am Acad Dermatol 1988; 18:115-122.
- Hodak E, Jones RE, Ackerman AB. Solitary keratoacanthoma is a squamous cell carcinoma; three examples with metastasis. Am J Dermatopath 1993;15:332-342.
- Piscioli F, Zumiani G, Boi S, Christofolini MA. A gigantic metastasizing keratoacanthoma. Report of a case and discussion of classification. Am J Dermtopath 1984;6:123-129.
- Grobb JJ, Suzini F, Richard MA, et al. Large keratoacanthomas treated with intralesional interferon alfa-2a. J Am Acad Dermatol 1993;29:237-241.
- Marks R, Foley P, Goodman G, et al. Spontaneous remission of solar keratoses: the case for conservative management. Br J Dermatol 1986;115:649-655.
- Dodson JM, DeSpain J, Hewett JE, Clark DP. Malignant potential of actinic keratoses and the controversy over treatment: a patient-orientated perspective. Arch Dermatol 1991;127:1029-1031.
- Marks R, Rennie G. Selwood TS. Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet 1988;1:795-797.
- Dubin N, Moseson M, Pasternack BS. Epidemiology of malignant melanoma: pigmentary traits, ultraviolet radiation, and the identification of high risk populations. Recent Results Cancer Res 1986;102:56-57.
- Chiarello SE. Full face cryotherapy (liquid nitrogen) peel. J Dermatol Surg Oncol 1992: 189:329-332.
- Holt PJ. Cryotherapy of skin cancer. Results of a 5 year period using liquid nitrogen spray cryosurgery. Br J Dermatol 1988;119:231-240.
- Collins PS. The chemical peel. Clin Dermatol 1987;5:57
- Humphreys TR, Werth V, Dzubow L, Kligman A. Treatment of photo-aged skin with trichloroacetic acid and topical Tretinoin. J Am Acad Dermatol 1996;34:638-44.
- Lawrence N, Cox SE, Cockerell CJ, et al. A comparison of the efficacy and safety of Jessner's solution and 35% trichloroacetic acid versus 5% 5-Fluorouracil in the treatment of widespread actinic keratoses. Arch Dermatol 1995;131:176-181.
- Swinehart JM. Salicylic acid ointment peeling of the hands and forearms. Effective non-surgical removal of pigmented lesion and actinic damage. J Dermatol Surg Oncol 1992;18:495-498.
- Bercovitch L. Topical chemotherapy of actinic keratoses of the upper extremities with Tretinoin and 5-fluorouracil. A double blinded controlled study. Br J Dermatol 1987;1116:549-552.
- Klein E, Stoll HL Jr, Milgram H, et al. Tumors of the skin. 12. Topical 5-fluorouracil for epidermal neoplasms. J Surg Oncol 1971;3:331-349.
- Unis ME. Short-term 5-fluorouracil treatment of actinic keratosis. Dermatol Surg 1995;21:162-3.
- Coleman WP 3rd, Yarborough JM, Mandy SH. Dermabrasion for prophylaxis and treatment of actinic keratoses. Dermatol Surg 1996;22:17-21.
- Fitzpatrick RE, Goldman JP, Ruiz-Esparza J. Clinical advantages of the carbon dioxide laser superpulsed mode. Treatment of verruca vulgaris, seborrheic keratoses. Lentigines and actinic cheilitis. J Dermatol Surg Oncol 1994;20:449-456.