eMedicine Specialties > Dermatology > Malignant Neoplasms

Squamous Cell Carcinoma: Follow-up

Author: Debjani Sahni, MBBS, MRCP, Cutaneous Oncology Fellow, Brigham and Women's Hospital, Dana Farber Cancer Institute
Coauthor(s): Chrysalyne D Schmults, MD, Instructor in Dermatology, Harvard Medical School; Director, Mohs Micrographic Surgery Center, Department of Dermatology, Brigham and Women's Hospital
Contributor Information and Disclosures

Updated: Mar 18, 2009

Follow-up

Further Outpatient Care

Low-risk tumors are usually cured with appropriate surgical therapy; however, patients who develop one squamous cell carcinoma (SCC) have a 40% risk of developing additional squamous cell carcinomas within the next 2 years. This risk is likely even greater as more time elapses. Thus, patients with a history of squamous cell carcinoma should be evaluated with a complete skin examination every 6-12 months.

Patients with high-risk tumors require skin and lymph node examinations at 3- to 6-month intervals for at least 2 years after diagnosis. In very high-risk cases, surveillance with CT scanning or MRI may be considered.

Deterrence/Prevention

General preventive measures

Prevention of squamous cell carcinoma is best accomplished by limiting exposure to UV radiation, including both natural sunlight and artificial sources of UV light such as tanning beds. Wearing protective clothing, limiting outdoor activities (especially between 10:00 am and 4:00 pm), and applying a broad-spectrum sunscreen (ie, one that blocks UVA and UVB light) with a sun protection factor of at least 15 every day all help reduce UV exposure.

Treatment of precancerous actinic keratoses (AKs) and in situ squamous cell carcinoma may prevent the future development of invasive squamous cell carcinoma. Additionally, Patient education regarding skin cancer warning signs and periodic self-directed and physician-directed complete skin examinations are recommended.

Chemoprevention

Chemoprevention with systemic retinoids is effective for reducing the number of new squamous cell carcinomas in both immunocompetent and immunosuppressed patients. Most recent studies have focused on the prophylactic use of oral acitretin, which has a relatively long half-life compared with isotretinoin. Low doses are often sufficient for prophylaxis. However, treatment must be continued indefinitely because a relapse in tumor development occurs following discontinuation of oral retinoids. Furthermore, systemic retinoids have not been shown to be beneficial in treating existing squamous cell carcinoma or at reducing the risk of recurrence after treatment.53

The mechanisms by which retinoids protect against the development of squamous cell carcinoma have not been fully elucidated. Data suggest that retinoids induce the expression of proapoptotic and antiproliferative genes, including TP53, caspases, and P73, in keratinocytes. The increase in epidermal Langerhans cells noted in one study suggests that retinoids may also enhance cutaneous immunosurveillance.54,55

Many patients are unable to tolerate the adverse effects associated with systemic retinoid therapy, although lower doses are better tolerated than higher doses. Organ transplant recipients (OTRs) appear to be more sensitive to the adverse effects of systemic retinoids compared with other patients. Adverse effects of systemic retinoids include mucocutaneous xerosis, dyslipidemia, liver function abnormalities, and teratogenicity.

Prognosis

Most squamous cell carcinomas are readily treated with an expectation of cure. Most large series in the literature have reported the risk of nodal or distant metastasis for primary tumors to be 2-6%.

A subset of squamous cell carcinoma carries an elevated risk of local recurrence, nodal or distant metastasis (usually to the lungs), and death. Tumors in this subset are termed high-risk squamous cell carcinoma (see below). However, prognostic models do not exist for squamous cell carcinoma. Because many of the risk factors below occur concurrently in single tumors and patients, determining which risk factors have the greatest prognostic significance is difficult. In the absence of prognostic models that take the presence of multiple risk factors into account, estimating risk for individual patients is based on very limited data and gestalt. Due to the lack of data, evidence-based decision making is often not possible. Subsequently, current management of high-risk squamous cell carcinoma varies widely.32,33

In one case series, the 3-year disease-specific survival rate for squamous cell carcinoma was estimated to be 85%. Survival rates approached 100% for lesions with no high-risk factors, but the disease-specific death rate was 30% for patients with at least 1 risk factor.56 These estimates derived from a case series may not be reflective of the risk for squamous cell carcinoma in general and may overestimate risk. However, the data highlight that a subset of squamous cell carcinomas do poorly (see below).

When squamous cell carcinoma does metastasize, it is usually occurs within 5 years from the time of diagnosis and involves the primary (ie, first echelon) draining lymph nodes. In general, metastasis from squamous cell carcinoma of the forehead, temples, eyelids, cheeks, and ears is to the parotid nodes; metastasis from squamous cell carcinoma of the lips and perioral region is primarily to the submental and submaxillary (upper cervical) nodes.

Once nodal metastasis of cutaneous squamous cell carcinoma has occurred, the overall 5-year survival rate has historically been in the range of 25-35%. Prognosis is extremely poor for patients with a compromised immune system, with metastasis to multiple lymph nodes, or with cervical lymph nodes greater than 3 cm in diameter. Nevertheless, data published in 2005 show that the combined use of surgery and adjuvant radiotherapy for patients with nodal metastasis increased the 5-year disease-specific survival rate to 73%.14 Metastasis to distant organs remains incurable. Thus, close surveillance and early detection of nodal metastasis can be life saving and is of paramount importance.

High-risk squamous cell carcinoma

A subset of squamous cell carcinoma is considered high risk because it has been associated with higher rates of recurrence, metastasis, and death in case series data. Squamous cell carcinoma can be characterized as high-risk by virtue of tumor-related factors (intrinsic factors), patient-related factors (extrinsic factors), or a combination of both.

Tumor-related factors in high-risk squamous cell carcinoma48  

Tumor-related factors are (1) tumor location (ie, lips, ears, within a scar), (2) tumor size greater than 2 cm (or 1.5 cm on ear or lip), (3), invasion to subcutaneous fat (or deeper), (4) poorly differentiated tumor cells, (5) recurrent tumor, and (6) perineural involvement.

Additionally, a prospective study of 210 patients with a diverse range of squamous cell carcinomas showed tumor-related factors were associated with adverse disease-specific survival using univariate analyses.56 Specifically, these factors were (1) local recurrence at presentation (P = .05), (2) invasion beyond subcutaneous tissue (P = .009), (3) depth in general (P = .05), (4) perineural invasion (P = .002), and (5) size greater than or equal to 4 cm (P = .0003).

Detailed information on tumor-related factors is as follows:

  • Location: The lips and the ears may have a higher rate of recurrent and metastatic disease than squamous cell carcinoma at other sites. The historical rates of metastases for squamous cell carcinoma of the external ear and the lip are approximately 11% and 10-14%, respectively.48 Numerous studies have demonstrated that the Marjolin ulcer subtype of squamous cell carcinoma behaves aggressively, with metastatic rates of approximately 18-38%. These are tumors that arise from a preexisting chronic wound. Similarly, invasive squamous cell carcinoma of the anogenital region carries a greater risk of metastasis. The poor prognosis of both the Marjolin ulcer and anogenital subtypes is likely related to delayed diagnosis.
  • Diameter: Lesions of invasive squamous cell carcinoma measuring less than 2 cm in diameter have been associated with a rate of metastasis of 9.1%, whereas those greater than 2 cm in diameter have a metastatic rate of up to 30.3%. A 2005 prospective study reported a 3-year disease-specific survival rate of 67% for lesions greater than 4 cm, compared with 93% for tumors smaller than 4 cm.56
  • Depth: Increased depth of invasion of squamous cell carcinoma is strongly associated with local recurrence, metastasis, and death. Squamous cell carcinoma with a depth of less than 2 mm rarely metastasizes. Squamous cell carcinoma with a depth of invasion of 2-4 mm has a historical recurrence rate of 5.3% and a metastasis rate of 6.7%. A 2008 prospective cohort study found a rate of metastasis of 4% for tumors of 2-6 mm thick. For tumors thicker than 6 mm, the risk increased to 16%.57
  • Cellular differentiation: More poorly differentiated tumors have a worse prognosis in cutaneous squamous cell carcinoma, with recurrence rates reported to be from 33-54%.48 The actual value of histologic grading alone, however, is less clear because poorly differentiated tumors that metastasize or recur also usually have other primary risk factors (eg, large diameter, deep invasion). Nonetheless, poorly differentiated squamous cell carcinomas are generally accepted to behave more aggressively.
  • Recurrent tumors: Local recurrence rates following extirpation of a recurrent squamous cell carcinoma range from 10-23%. Reported rates of metastasis are as high as 25-45%, but these figures may overestimate the risk in recurrences that are caught early.
  • Perineural invasion: Perineural invasion has been estimated to occur in 2.4% of persons with cutaneous squamous cell carcinoma. The prognosis in such cases is worse, with historical rates of metastasis reported to be as high as 47%. Much lower rates of metastasis (8%) have been reported using MMS.48 The degree of nerve involvement likely has a large impact on prognosis. Involvement of major (ie, named) nerve branches carries a very high risk of recurrence, metastasis, and death. The risks are substantially decreased when tumor-free margins are painstakingly obtained by removal of the involved nerve. However, the prognosis is still guarded. One study showed the diameter of involved nerves to significantly impact outcomes, with no disease-specific deaths occurring in those with involvement of nerves less than 0.1 mm in diameter, compared to 32% of patients dying from disease when nerves 0.1 mm or larger were involved.58  

Patient-related factors in high-risk squamous cell carcinoma

General patient-related factors are (1) organ transplant recipient, (2) hematologic malignancy (eg, CLL), (3) long-term immunosuppressive therapy, and (4) HIV infection or AIDS.

Detailed information on patient-related factors is as follows:

  • Organ transplant recipients
    • A 65-fold increased risk of squamous cell carcinoma exists in OTRs. This correlates with the intensity of immunosuppression, so that heart transplant recipients have 3 times the risk of squamous cell carcinoma compared with kidney transplant recipients.59 However, although the proportion of heart transplant recipients developing new tumors is greater than in kidney transplant recipients, the mean number of tumors per patient is higher in kidney transplant recipients. This could be explained by a longer duration of immunosuppression in patients who are younger at transplantation.
    • Additionally, OTRs have a high risk of developing further squamous cell carcinomas, with 66% of OTRs developing a second squamous cell carcinoma within 5 years of their first squamous cell carcinoma diagnosis.60
    • In addition to squamous cell carcinomas being a more frequent occurrence in OTRs, the tumors can be clinically very aggressive. In one study of cardiothoracic transplant recipients (heart or heart-lung transplants), 4% of patients developed aggressive cutaneous squamous cell carcinoma within 10 years of transplantation. The majority (15 of 18) were poorly differentiated, and two thirds of the patients with aggressive squamous cell carcinoma had distant-organ metastases or died of their disease.61
  • CLL: Squamous cell carcinoma arising in patients with CLL and small lymphocytic lymphoma (SLL) also carries a worse prognosis. For example, in patients with CLL, the recurrence rate of squamous cell carcinoma treated with MMS was 7-fold higher at 5 years compared with patients without CLL.62 One study found that squamous cell carcinomas in CLL and SLL patients are often multiple (67%), high grade (56%), and with a high risk of recurrence and metastasis (25%) and death from disease (41%).63
  • HIV infection: HIV infection and AIDS are not definitively associated with high-risk squamous cell carcinoma. An increased incidence of anal and penile squamous cell carcinoma associated with human papillomavirus (HPV) has been reported in HIV patients. A high risk of recurrence has been reported after desiccation and curettage.64 A small series reported cases of aggressive cutaneous squamous cell carcinoma in HIV patients, with a 50% mortality rate at 7 years.7

Other reported conditions associated with aggressive squamous cell carcinoma

  • Bullous diseases: The risk of squamous cell carcinoma in patients with bullous disease is markedly elevated. The risk of death is particularly high in those with epidermolysis bullosa, with an 80% mortality rate 5 years after diagnosis of first primary squamous cell carcinoma.
  • Arsenic exposure
  • PUVA exposure

Patient Education

Patients should be counseled to avoid excessive UV radiation by limiting outdoor activity to early morning and late afternoon, using protective clothing, and wearing a broad-brimmed hat to shade the head and the neck area. Use of artificial tanning devices should be strongly discouraged because this has been associated with a 2.5-fold increase in the risk of developing squamous cell carcinoma. Daily application of a broad-spectrum sunscreen with a sun protection factor of at least 15 should also be encouraged. These measures are critically important for patients who are immunosuppressed, and they should be an integral part of the educational program for patients who have recently undergone organ transplantation.

Counseling patients regarding treatment of areas of chronic skin inflammation or trauma is important in preventing the future development of squamous cell carcinoma at those sites.

For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Additionally, see eMedicine's patient education articles Skin Cancer and Skin Biopsy. For information on cancer risk, prevention, and screening, see the AT-RISC Alliance and the International Transplant Skin Cancer Collaborative. For more information about MMS, see the American College of Mohs Surgery.

Miscellaneous

Medicolegal Pitfalls

Malpractice suits are uncommon following the diagnosis and treatment of squamous cell carcinoma because, in most cases, both are straightforward and readily accomplished. Nonetheless, squamous cell carcinoma is a lesion with the potential to cause substantial morbidity and even mortality, and physicians who diagnose and treat squamous cell carcinoma are held legally accountable for actions that are taken (or not taken) that fall outside the standard of care.

Failure to diagnose squamous cell carcinoma may lead to substantial morbidity and occasionally mortality. Large court awards have been set for cases in which failure to diagnose squamous cell carcinoma has led to death.

Failure to treat and perceived inadequate treatment are common causes of malpractice claims against physicians. These cases occur most frequently when physicians fail to use an adequately aggressive primary treatment or fail to recognize a high-risk lesion. Recognizing that high-risk squamous cell carcinoma may metastasize and lead to death is important. Therefore, appropriately aggressive and prompt treatment is indicated in such cases. However, because defined prognostic criteria and models have not been developed, little information is available to guide clinicians in the most appropriate staging and treatment for individuals with high-risk squamous cell carcinoma. Because of a lack of data, care standards regarding nodal staging, radiologic imaging, and postsurgical adjuvant therapy have not been developed. Subsequently, a lack of uniformity exists among experienced physicians in the treatment of high-risk squamous cell carcinoma.32,33

Failure to provide appropriate follow-up is a potential pitfall. The courts hold the physician, not the patient, responsible for appropriate follow-up. Because primary treatment of squamous cell carcinoma is not a guarantee of cure, ensuring adequate patient follow-up is essential. Failure to inform patients of the potential morbidity associated with squamous cell carcinoma may lead to the lesion being regarded as trivial and not requiring follow-up. Missed appointments may indicate the patient is worried or angry. Thus, patients with a history of squamous cell carcinoma who miss follow-up appointments should be contacted by phone (or when necessary, with a certified letter) to reschedule. All medical staff are advised to document phone calls in writing and to save certified letter documentation.

Failure to explain all possible risks and complications of surgery is another legal pitfall. Surgery for squamous cell carcinoma may cause bleeding, infection, scar formation, physical deformity, and nerve damage. The removal of deeply invasive lesions may lead to substantial morbidity, including paralysis and pain syndromes. Explaining all possible risks prior to surgery is essential. Such explanations should ideally be documented in written consent forms signed by the treating physician and the patient. Additionally, the physician should not treat lesions outside the realm of his or her comfort zone. If a surgical complication develops, the physician who performed the primary procedure is held legally responsible, regardless of who handles the complication.

 
Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Stephen D Hess, MD, PhD, and Glenn Goldman, MD, to the development and writing of this article.



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References
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Keywords

squamous cell carcinoma, skin cancer, SCC, actinic keratoses, SCC in situ, Bowen disease, Bowen's disease, keratotic invasive SCC, leukoplakia, erythroplasia of Queyrat, nodular SCC, periungual SCC, Marjolin ulcer, actinically derived SCC, adenoid squamous cell carcinoma, ASCC, adenosquamous cell carcinoma, verrucous carcinoma,  keratoacanthoma,  oral florid papillomatosis, epithelioma cuniculatum, giant condyloma of Buschke and Löwenstein, malignant tumor of keratinocytes, sun-induced cancerous lesions

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Contributor Information and Disclosures

Author

Debjani Sahni, MBBS, MRCP, Cutaneous Oncology Fellow, Brigham and Women's Hospital, Dana Farber Cancer Institute
Debjani Sahni, MBBS, MRCP is a member of the following medical societies: British Association of Dermatologists, Royal College of Physicians, and St John's Dermatological Society
Disclosure: Nothing to disclose.

Coauthor(s)

Chrysalyne D Schmults, MD, Instructor in Dermatology, Harvard Medical School; Director, Mohs Micrographic Surgery Center, Department of Dermatology, Brigham and Women's Hospital
Chrysalyne D Schmults, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Micrographic Surgery and Cutaneous Oncology, American Society for Dermatologic Surgery, and International Society for Dermatologic Surgery
Disclosure: Nothing to disclose.

Medical Editor

R Stan Taylor, MD, Professor of Dermatology, University of Texas Southwestern Medical School; Director of Skin Surgery and Oncology Clinic, Department of Dermatology, University of Texas Southwestern Medical Center
R Stan Taylor, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery, American Dermatological Association, American Medical Association, American Society for Dermatologic Surgery, Christian Medical & Dental Society, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Mary Farley, MD, Dermatologic Surgeon/Mohs Surgeon, Anne Arundel Surgery Center
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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