112: Squamous Cell Carcinoma and Keratoacanthoma Flashcards
What are four high risk features for local recurrence and metastasis of squamous cell carcinoma (SCC)?
- Tumor thickness greater than 2 mm
- Clark level higher than IV
- Perineural invasion
- Lip or ear as primary site
What is the 5-year metastatic rate of squamous cell carcinoma (SCC)?
The 5-year metastatic rate of SCC is generally low, approximately 5%.
What are two geographic factors affecting the incidence of squamous cell carcinoma (SCC)?
- Inverse association with latitude
- Increased incidence in sun-exposed areas
What is the predominant etiologic risk factor for skin carcinogenesis?
Cumulative lifetime exposure to ultraviolet (UV) radiation is the predominant etiologic risk factor for skin carcinogenesis.
How does the incidence of squamous cell carcinoma (SCC) vary with sex?
The incidence of SCC is higher in males compared to females.
How does the incidence of squamous cell carcinoma (SCC) vary with race?
The incidence of SCC is approximately 3-fold less common in Blacks as compared to Whites.
What are the primary modes of therapy for localized squamous cell carcinoma (SCC)?
The primary mode of therapy for localized SCC is complete surgical excision, preferably microscopically controlled surgery (Mohs surgery).
What are the nonsurgical interventions for locally advanced, unresectable, or metastatic squamous cell carcinoma (SCC)?
Nonsurgical interventions include:
1. Radiation therapy
2. Systemic treatment with chemotherapy or targeted therapy
What is the role of niacinamide in the prevention of squamous cell carcinoma (SCC)?
Niacinamide is given at a dose of 500 mg as chemoprevention for SCC.
What are the topical therapeutic options for squamous cell carcinoma (SCC)?
- Topical chemotherapy agents (e.g., 5-fluorouracil)
- Imiquimod
- Photodynamic therapy
What is the significance of immunosuppression in the incidence of squamous cell carcinoma (SCC)?
Immunosuppressed patients have a 65-fold to 250-fold increased incidence of SCC compared to immunocompetent individuals.
What is the relationship between latitude and the incidence of squamous cell carcinoma (SCC)?
The closer to the equator, the higher the incidence of SCC in white individuals, with similar gradients for both genders and all ages.
How does age affect the incidence of squamous cell carcinoma (SCC)?
SCC incidence increases with age, primarily affecting individuals 60 years of age and older, due to cumulative lifetime exposure to UVR being a predominant risk factor.
What is the significance of UVR exposure in the development of squamous cell carcinoma (SCC)?
UVR exposure is recognized as the most important environmental risk factor for the development of SCC, with a strong dose-response association and specific UV signature mutations being a major contributor.
What are the precursor lesions associated with squamous cell carcinoma (SCC)?
SCCs typically arise from basal keratinocytes of the interfollicular epidermis, with most invasive SCCs developing from preinvasive lesions such as actinic keratosis (AK) or Bowen disease.
What genetic factors predispose individuals to squamous cell carcinoma (SCC)?
Genetic predisposition includes light skin complexion, variations in the melanocortin-1 receptor, single-nucleotide polymorphisms in pigmentation genes, and inherited defects in DNA repair mechanisms.
What are the implications of albinism in relation to squamous cell carcinoma (SCC)?
Albinism is associated with a high risk for SCC, even in black individuals, highlighting the relationship between skin carcinogenesis and sun exposure, as well as the protective effect of eumelanin.
What are the environmental risk factors for squamous cell carcinoma (SCC)?
Environmental risk factors include UVR exposure, arsenic in medications and water, and cutting oils in industrial occupations, all of which can stimulate skin carcinogenesis.
What is the estimated cumulative lifetime risk of developing SCC among patients with multiple actinic keratosis (AK)?
The estimated cumulative lifetime risk among patients with multiple AK is approximately 6% to 10%.
What is the relationship between UVR exposure and the incidence of squamous cell carcinoma (SCC) in different populations?
The incidence of SCC is higher in populations with greater UVR exposure, such as Australians, who have a reported rate of 387 per 100,000 person-years.
What role does genetic predisposition play in the risk of developing squamous cell carcinoma (SCC)?
Genetic predisposition significantly influences SCC risk. Individuals with light skin complexions and specific genetic variations, such as those in the melanocortin-1 receptor, are at higher risk.
What are the immunosuppressive effects of UVR that contribute to the development of squamous cell carcinoma (SCC)?
UVR exposure leads to immunosuppressive effects that promote SCC development, including:
1. Depletion of Langerhans cells from the epidermis.
2. Improper antigen presentation in skin-draining lymph nodes.
How does immunosuppression affect the risk of developing SCC in organ transplant recipients?
Immunosuppression significantly increases the risk of developing SCC in organ transplant recipients (OTRs), with SCC being the most frequent malignancy in these patients.
What role do photosensitizing drugs play in the risk of developing SCC?
The chronic use of photosensitizing drugs, such as antibiotics and triazole antifungals, increases the risk for SCC, particularly in patients with sun-sensitive skin types.
What is the relationship between HPV and the development of SCC?
HPVs are proposed to be possible cocarcinogens in the development of SCC, particularly in sun-exposed skin.
What is the significance of beta-HPV in the development of SCC?
Beta-HPV is believed to play a role in the initiation of SCC, particularly in sun-exposed skin, but may not be necessary for tumor maintenance.
What are the chronic inflammatory conditions that may predispose individuals to the development of squamous cell carcinoma (SCC)?
Chronic inflammatory conditions that may predispose to SCC include:
1. Discoid lupus erythematodes
2. Lichen ruber mucosae
3. Lichen sclerosus
4. Dystrophic epidermolysis bullosa
How does the mutation of the TP53 gene contribute to the pathogenesis of squamous cell carcinoma (SCC)?
Mutations in the TP53 gene lead to a loss of its tumor-suppressor function, which is crucial for responding to UV damage.
What is the significance of RAS mutations in the development of squamous cell carcinoma (SCC)?
RAS mutations are implicated in the initiation of SCC, with data indicating that 21% of SCCs harbor activating mutations in RAS genes.
What are the clinical presentations of squamous cell carcinoma (SCC)?
The clinical presentation of SCC is variable and depends on the histologic subtype and location of the tumor.
What are the typical clinical findings of Squamous Cell Carcinoma (SCC)?
Typical clinical findings of SCC include:
- Slowly enlarging, firm, skin-colored to erythematous plaques or nodules with marked hyperkeratosis.
- Ulceration, exophytic, or infiltrative growth patterns.
Where do Squamous Cell Carcinomas (SCCs) typically arise?
SCCs typically arise in sun-exposed areas such as the face, head, and neck, often on a background of actinic keratosis (AK) or Bowen disease.
What are the typical clinical findings of Squamous Cell Carcinoma (SCC)?
Typical clinical findings of SCC include slowly enlarging, firm, skin-colored to erythematous plaques or nodules with marked hyperkeratosis, ulceration, exophytic, or infiltrative growth patterns.
What are the special locations where Oral SCC may arise?
Oral SCC may arise on apparently normal mucosa and is usually preceded by leukoplakia, erythroplakia, or leukoerythroplakia.
What are the typical presentations of Oral SCC?
Typical presentations include tumors with a whitish surface or ulcers with elevated indurated borders, and exophytic or endophytic growth patterns with subsequent ulcer formation.
What should the standard histopathology report for SCC include?
The report should include histologic subtype, grade of differentiation, maximum vertical tumor diameter, extent of dermal invasion, and presence or absence of perineural, vascular, or lymphatic invasion.
What are the basic histopathologic features of SCC?
Basic features include atypical keratinocytes originating in the epidermis and infiltrating into the dermis, with varying degrees of differentiation.
What characterizes Well-differentiated SCC?
Well-differentiated SCC shows minimal pleomorphism, prominent keratinization, parakeratosis, individual cell dyskeratosis, and horn pearl formation.
What characterizes Poorly differentiated SCC?
Poorly differentiated SCC has pleomorphic nuclei with high atypia, frequent mitoses, and very few areas of keratinization.
What are the histopathologic variants of SCC?
Variants include Spindle Cell SCC, Acantholytic SCC, and Verrucous SCC, each with distinct characteristics.
What are the high-risk features for staging cutaneous SCC?
High-risk features include thickness >2 mm, Clark level >IV, perineural invasion, primary site being the lip or ear, and poorly or undifferentiated tumors.
What is the primary mode of therapy for localized cutaneous SCC?
The primary mode of therapy is surgical excision, preferably Mohs surgery, which has a cure rate of 95%.
What distinguishes Desmoplastic SCC from other variants?
Desmoplastic SCC is characterized by a highly infiltrative growth pattern with abundant mucinous stroma and is often associated with perineural or perivascular infiltration.
What are the characteristics of Keratoacanthoma (KA)?
KA is characterized by a symmetric aspect, large strands of monomorphic keratinocytes, and surrounding inflammatory infiltrate.
What is the N staging for a patient with SCC and a single ipsilateral lymph node measuring 7 cm?
The N staging is N3 because it involves a single ipsilateral lymph node larger than 6 cm.
What is the histopathologic variant for a tumor on an amputation stump?
The tumor is classified as Verrucous SCC.
What is the N staging for a patient with SCC and a single ipsilateral lymph node measuring 3 cm?
The N staging is N1 because it involves a single ipsilateral lymph node smaller than 3 cm.
What is the T staging for a tumor on the lower lip with Clark level IV invasion?
The tumor is classified as T2 because it has at least one high-risk feature (Clark level IV invasion).
What is the histopathologic variant for a tumor on the oral cavity resembling oral florid papillomatosis?
The tumor is classified as Verrucous SCC.
What is the T staging for a 65-year-old male with a 3 cm tumor on the lower lip with perineural invasion?
The tumor is classified as T2 because it is larger than 2 cm and has at least one high-risk feature (perineural invasion).
What is the histopathologic variant for a biopsy revealing pseudoglandular structures and extensive acantholysis?
The tumor is classified as Acantholytic (Adenoid) SCC.
What is the T staging for a 70-year-old patient with a 1.5 cm tumor on the ear with Clark level IV invasion?
The tumor is classified as T1 because it is smaller than 2 cm but has fewer than 2 high-risk features.
What is the likely diagnosis for a rapidly growing nodule on the hand that regressed spontaneously?
The likely diagnosis is Keratoacanthoma (KA), a highly differentiated variant of SCC.
What is the T staging for a tumor invading the orbit?
The tumor is classified as T3 because it invades the orbit.
What is the T staging for a patient with a 1 cm tumor on the lip with 3 mm thickness?
The tumor is classified as T1 because it is smaller than 2 cm and has fewer than 2 high-risk features.
What is the N staging for a patient with SCC and metastasis in a single ipsilateral lymph node measuring 3.5 cm?
The N staging is N2a because it involves a single ipsilateral lymph node larger than 3 cm but smaller than 6 cm.
What is the histopathologic variant for a tumor on the plantar skin resembling epithelioma cuniculatum?
The tumor is classified as Verrucous SCC.
What is the T staging for a patient with SCC and a tumor invading the skull base?
The tumor is classified as T4 because it invades the skull base.
What is the T staging for a patient with a 1 cm tumor with 1.5 mm thickness and Clark level III invasion?
The tumor is classified as T1 because it is smaller than 2 cm and has fewer than 2 high-risk features.
What is the N staging for a patient with SCC and metastasis in multiple ipsilateral lymph nodes, each measuring 2 cm?
The N staging is N2b because it involves multiple ipsilateral lymph nodes, each smaller than 3 cm.
What is the histopathologic variant for a tumor on the genitoanal region resembling giant condyloma acuminatum?
The tumor is classified as Verrucous SCC.
What is the N staging for a patient with SCC and metastasis in contralateral lymph nodes measuring 6 cm?
The N staging is N3 because it involves contralateral lymph nodes larger than 6 cm.
What is the N staging for a patient with SCC and metastasis in a single contralateral lymph node measuring 3.5 cm?
The N staging is N2c because it involves a single contralateral lymph node larger than 3 cm but smaller than 6 cm.
What is the T staging for a patient with SCC and a tumor on the lower lip with perineural invasion?
The tumor is classified as T2 because it has at least one high-risk feature (perineural invasion).
What is the N staging for a patient with SCC and metastasis in a single ipsilateral lymph node measuring 2 cm?
The N staging is N1 because it involves a single ipsilateral lymph node smaller than 3 cm.
What is the T staging for a patient with SCC and a tumor on the ear with poorly differentiated histology?
The tumor is classified as T2 because it has at least one high-risk feature (poor differentiation).
What is the N staging for a patient with SCC and metastasis in multiple contralateral lymph nodes, each measuring 2 cm?
The N staging is N2c because it involves multiple contralateral lymph nodes, each smaller than 3 cm.
What is the T staging for a patient with SCC and a tumor on the lower lip with Clark level III invasion?
The tumor is classified as T1 because it has fewer than 2 high-risk features.
What is the N staging for a patient with SCC and metastasis in a single contralateral lymph node measuring 7 cm?
The N staging is N3 because it involves a single contralateral lymph node larger than 6 cm.
What is the T staging for a patient with SCC and a tumor on the ear with Clark level IV invasion?
The tumor is classified as T2 because it has at least one high-risk feature (Clark level IV invasion).
What is the N staging for a patient with SCC and metastasis in a single ipsilateral lymph node measuring 6 cm?
The N staging is N2a because it involves a single ipsilateral lymph node larger than 3 cm but smaller than 6 cm.
What is the T staging for a patient with SCC and a tumor on the lower lip with poorly differentiated histology?
The tumor is classified as T2 because it has at least one high-risk feature (poor differentiation).
What is the N staging for a patient with SCC and metastasis in multiple ipsilateral lymph nodes, each measuring 3 cm?
The N staging is N2b because it involves multiple ipsilateral lymph nodes, each smaller than 3 cm.
What is the T staging for a patient with SCC and a tumor on the ear with perineural invasion?
The tumor is classified as T2 because it has at least one high-risk feature (perineural invasion).
What is the N staging for a patient with SCC and metastasis in a single contralateral lymph node measuring 2 cm?
The N staging is N2c because it involves a single contralateral lymph node smaller than 3 cm.
What is the T staging for a patient with SCC and a tumor on the lower lip with 3 mm thickness?
The tumor is classified as T1 because it has fewer than 2 high-risk features.
What is the N staging for a patient with SCC and metastasis in multiple contralateral lymph nodes, each measuring 3 cm?
The N staging is N2c because it involves multiple contralateral lymph nodes, each smaller than 3 cm.
What is the T staging for a patient with SCC and a tumor on the ear with 3 mm thickness?
The tumor is classified as T1 because it has fewer than 2 high-risk features.
What is the N staging for a patient with SCC and metastasis in a single ipsilateral lymph node measuring 2.5 cm?
The N staging is N1 because it involves a single ipsilateral lymph node smaller than 3 cm.
What is the T staging for a patient with SCC and a tumor on the lower lip with Clark level IV invasion?
The tumor is classified as T2 because it has at least one high-risk feature (Clark level IV invasion).
What is the N staging for a patient with SCC and metastasis in a single contralateral lymph node measuring 3 cm?
The N staging is N2c because it involves a single contralateral lymph node smaller than 3 cm.
What are the histopathologic features of Desmoplastic SCC?
Desmoplastic SCC is characterized by a highly infiltrative growth pattern with abundant mucinous stroma surrounding the tumor cells.
What are the clinical implications of Desmoplastic SCC?
It is often associated with perineural or perivascular infiltration, leading to a high rate of recurrence and metastases.
How does the grading system for cutaneous SCC influence treatment decisions?
The grading system is crucial for assessing the risk of recurrence and metastasis, influencing treatment options based on the grade.
What characterizes desmoplastic SCC?
Desmoplastic SCC is characterized by a highly infiltrative growth pattern with abundant mucinous stroma surrounding the tumor cells. It is often associated with perineural or perivascular infiltration, leading to a high rate of recurrence and metastases.
How does the grading system for cutaneous SCC influence treatment decisions?
The grading system for cutaneous SCC ranges from G1 (well differentiated) to G4 (undifferentiated) and is crucial for assessing the risk of recurrence and metastasis. Higher grades (G3 and G4) indicate a greater likelihood of aggressive behavior, influencing the choice of treatment.
What are the key features that classify cutaneous SCC as high-risk according to the AJCC staging system?
Key features that classify cutaneous SCC as high-risk include thickness >2 mm, Clark Level >IV, presence of perineural invasion, primary site on lip or ear, and poorly or undifferentiated differentiation.
What is the significance of lymph node involvement in the prognosis of cutaneous SCC?
Lymph node involvement in cutaneous SCC significantly increases the risk of recurrence and mortality, especially in high-risk tumors. The TNM/UICC classification categorizes lymph node involvement into groups based on size and number of involved nodes.
What are the primary treatment options for localized cutaneous SCC?
The primary treatment option for localized cutaneous SCC is surgical excision, preferably using Mohs surgery, which has a cure rate of 95%.
What are the conventional treatment options for low-risk squamous cell carcinoma (SCC)?
Conventional standard excision with 4-to-6-mm margins may be acceptable as primary treatment for local, low-risk SCCs.
What is the role of topical therapy in the treatment of SCC?
Topical therapies such as imiquimod, 5-fluorouracil, cryotherapy, and photodynamic therapy have been reported for SCC. However, evidence for their efficacy is limited and generally not regarded as appropriate for invasive SCC.
What is the significance of radiation therapy in the management of SCC?
Radiation therapy may serve as an alternative to surgery in the primary treatment of superficially invasive, small SCCs in low-risk areas.
What are the challenges associated with systemic treatment of locally advanced and metastatic SCC?
Locally advanced, unresectable, or metastatic SCC presents a therapeutic challenge due to limited available data on systemic therapy, with only approximately 30% of patients responding to standard treatment.
What are the potential benefits of targeted therapy in SCC?
Targeted therapy strategies targeting the EGFR, such as small molecules or antibodies, may provide nonsurgical options for advanced SCC, with a reported 29% response rate for cetuximab.
What factors influence the prognosis of SCC?
The majority of SCCs are low risk and present with early-stage disease, resulting in a high cure rate. However, prognosis for locally advanced SCC is generally poor.
What is the relationship between local recurrence and metastasis in SCC?
Local recurrence may indicate failure to completely treat the primary tumor or local metastasis and often precedes metastasis.
What is the risk of developing metastasis from SCC?
The risk of developing metastasis from SCC is generally low, with a 5-year metastatic rate of 5%. However, certain subgroups, like organ transplant recipients, have a significantly higher risk.
What is the recommended change in immunosuppressive regimen for organ transplant recipients developing multiple SCCs?
A dose reduction of calcineurin inhibitors or antimetabolites in favor of mTOR inhibitors is recommended.
What are the recommended treatment options for low-risk SCC and how does local in-transit metastasis affect treatment decisions?
For low-risk SCC, conventional standard excision with 4-to-6-mm margins is acceptable. Local in-transit metastasis may necessitate wide surgical excision or irradiation.
What is the role of topical therapy in the treatment of invasive SCC?
Topical therapies such as imiquimod, 5-fluorouracil, cryotherapy, and photodynamic therapy have been reported for SCC, but their efficacy is limited.
How does the prognosis differ for patients with locally advanced SCC compared to those with early-stage disease?
The prognosis for locally advanced SCC is generally poor, while early-stage disease has a high cure rate and excellent prognosis.
What factors contribute to a higher risk of metastasis in SCC?
Factors contributing to a higher risk of metastasis include immunosuppression, greater tumor burden, and more aggressive tumor behavior.
What is the significance of local recurrence in SCC?
Local recurrence may indicate failure to completely treat the primary tumor and is a key indicator of aggressive behavior.
What are key factors for the prevention of SCC?
Sun avoidance and close dermatologic surveillance of high-risk individuals are key factors for the prevention of SCC.
What is the preventive effect of sunscreens in relation to SCC?
The preventive effect of sunscreens with high SPF and broad UVA/UVB coverage is well established.
What is the role of niacinamide in the prevention of NMSC?
Niacinamide is suitable for chemoprevention of NMSC, protecting keratinocytes against UV-induced damage.
How effective is high-dose oral 13-cis retinoic acid in reducing new skin cancers in xeroderma pigmentosum patients?
Patients treated with high-dose oral 13-cis retinoic acid for 2 years experienced a 63% reduction in new skin cancers.
What changes in immunosuppressive regimens are recommended for organ transplant recipients at risk of SCC?
For organ transplant recipients at risk of SCC, a change in the immunosuppressive regimen is recommended.
What are the risk factors for the development of squamous cell carcinoma?
Risk factors include carcinoma in situ, physical and chemical carcinogens, genetic predisposition, immunosuppression, drugs, and chronic inflammation.
What are the key features included in the histopathology report for cutaneous squamous cell carcinoma diagnosis?
Key features include histologic subtype, grading, maximum tumor thickness, Clark level, perineural invasion, vascular/lymphatic invasion, complete excision, and minimum margins.
What is the staging classification for cutaneous squamous cell carcinoma according to the AJCC?
The staging classification includes Tx, T0, Tis, T1, T2, T3, T4, Nx, N0, N1, N2a, N2b, N2c, M0, and M1.
What are some examples of drugs that can cause skin issues?
Drugs include doxycycline, fluorouracil, and tizanidine antifungals.
What are targeted therapies for skin conditions?
Targeted therapies include BRAF/MEK inhibitors.
What are the key features of chronic inflammation and chronic injury of the skin?
Key features include chronic ulcers, discoid lupus erythematosus, lichen ruber mucinosus, lichen sclerosus, lupus vulgaris, and infection with human papillomavirus (HPV).
What are the histologic subtypes for cutaneous squamous cell carcinoma?
Histologic subtypes include common, verrucous, desmoplastic, acantholytic, spindle-cell, and other.
How is the grading of cutaneous squamous cell carcinoma determined?
Grading includes well differentiated, moderately differentiated, poorly differentiated, undifferentiated, and cannot be assessed.
What is the maximum tumor thickness for cutaneous squamous cell carcinoma?
Maximum tumor thickness is measured in mm.
What is the Clark level for cutaneous squamous cell carcinoma?
Clark level is level IV or less.
What is perineural invasion in cutaneous squamous cell carcinoma?
Perineural invasion can be either Yes or No.
What is vascular/lymphatic invasion in cutaneous squamous cell carcinoma?
Vascular/lymphatic invasion can be either Yes or No.
What does complete excision mean in cutaneous squamous cell carcinoma?
Complete excision can be either Yes or No.
What is the minimum lateral margin in cutaneous squamous cell carcinoma?
Minimum lateral margin is measured in mm.
What is the minimum deep margin in cutaneous squamous cell carcinoma?
Minimum deep margin is measured in mm.
How is the staging of primary tumor (T) for cutaneous squamous cell carcinoma determined?
Staging includes T0 (no evidence of primary tumor), Tis (carcinoma in situ), T1 (tumor ≤2 cm with fewer than 2 high-risk features), T2 (tumor >2 cm or any size with 2 or more high-risk features), T3 (tumor with invasion of maxilla, mandible, orbit, or temporal bone), and T4 (tumor with invasion of skeleton or perineural invasion of skull base).
What are the low risk and high risk factors for local recurrence or metastases in squamous cell skin cancer?
Low risk factors include area < 20 mm², no prior RT or chronic inflammatory process, no immunosuppression, no rapidly growing tumor, no neurologic symptoms, well-differentiated pathology, and depth/thickness ≤ 5 mm with no invasion beyond subcutaneous fat. High risk factors include area ≥ 20 mm², prior RT or chronic inflammatory process, immunosuppression, rapidly growing tumor, neurologic symptoms, poorly differentiated pathology, and depth/thickness > 6 mm or invasion beyond subcutaneous fat.
What syndromes are associated with a predisposition to squamous cell carcinoma?
Associated syndromes include Squamous Cell Carcinoma (BLM, RECQL3), Bloom syndrome (DKC1, TERT, TINF2, NHP2/NOLA2), Dyskeratosis congenita (ERCC1, WRN, EXOSC3), Epidermolysis bullosa (COL7A1), Xeroderma pigmentosum (XPA, XPC, XPD, XPE, XPF, XPV), and Keratoacanthoma (MSH2, MSH6).
What are the genes associated with Basal cell nevus syndrome?
Genes include BLM and PTCH1, which are involved in the maintenance of chromosomal stability.
What are the genes associated with Dyskeratosis congenita?
Genes include DKC1, TERC, TINF2, NHP2/NOLA2, which are involved in telomere homeostasis and trafficking of telomerase.
What is the gene associated with Epidermolysis bullosa?
The gene is COL7A1, which is responsible for anchoring the epidermis to the dermis.
What are the genes associated with Fanconi anemia?
Genes include FANCA, FANCB, FANCC, FANCD2, FANCI, FANCL, FANCM, FANCR, which are involved in melanosomal and lysosomal storage.
What are the genes associated with Xeroderma pigmentosum?
Genes include XPC, XPD, XPB, XPE, XPF, XPG, which are involved in nucleotide excision repair.
