Characteristics of the major hereditary syndromes associated with a predisposition to SCC are described in Table 4 below.
Table 4. Hereditary Syndromes Associated with Squamous Cell Carcinoma of the Skin
a For more information on genetic testing laboratories, see GeneTests: Laboratory Directory.
|Condition ||Gene(s) ||Clinical Testing Availabilitya||Pathway|
|Xeroderma pigmentosum (complementation group A, group B, group C, group D, group E, group F, and group G) ||XPA, XPB/ERCC3, XPC, XPD/ERCC2, XPE/DDB2 , XPF/ERCC4, XPG/ERCC5||XPA, XPC||Nucleotide excision repair|
|Xeroderma pigmentosum variant||POLH (XP-V)||No||Error-prone polymerase|
|Multiple self-healing squamous epithelioma (Ferguson-Smith syndrome) ||MSSE||No||Unknown|
|Oculocutaneous albinism (type IA, type IB, type II, type III, and type IV)||TYR, OCA2, MATP/OCA4, TYRP1||TYR, OCA2, TYRP1||Melanin synthesis|
|Hermansky-Pudlak syndrome||HPS1, HPS3, HPS4, HPS5, HPS6, HPS7/DTNBP1, HPS8/BLOC1S3||HPS1, HPS3, HPS4, HPS7||Melanosomal and lysosomal storage|
|Hermansky-Pudlak syndrome, Type 2||AP3B1||No||Melanosomal and lysosomal storage|
|Chediak-Higashi syndrome||LYST||LYST||Lysosomal transport regulation|
|Griscelli syndrome (type 1, type 2, and type 3)||MYO5A, RAB27A, MLPH||RAB27A||Pigment granule transport|
|Elejalde Disease||MYO5A||No||Pigment granule transport|
|Dystrophic epidermolysis bullosa (dominant and autosomal recessive subtypes) ||COL7A1||COL7A1||Collagen anchor of basement membrane to dermis|
|Junctional epidermolysis bullosa||LAMA3, LAMB3, LAMC2 , COL17A1||LAMA3, LAMB3, LAMC2, COL17A1||Connective tissue|
|Epidermodysplasia verruciformis||EVER1 , EVER2||No||Signal transduction in endoplasmic reticulum|
|Fanconi anemia||FANCA, FANCB, FANCC, FANCD1/BRCA2, FANCD2, FANCE, FANCF, FANCG/XRCC9, FANCI, FANCJ/BRIP1, FANCL, FANCM, FANCN/PALB2||Chromosomal breakage testing; BRIP1, FANCA, FANCC, FANCE, FANCF, FANCG, PALB2||DNA repair|
|Dyskeratosis congenita||DKC1, TERC, TINF2, NHP2/NOLA2, NOP10/NOLA3, TERT,WRAP53, C16orf57||DKC1, TERC, TINF2, NHP2, NOP10, TERT||Telomere maintenance and trafficking|
|Rothmund-Thomson syndrome||RECQL4, C16orf57||RECQL4||Chromosomal stability|
|Bloom syndrome||BLM/RECQL3||Sister chromatid exchange, BLM||Chromosomal stability|
|Werner syndrome||WRN/RECQL2||No||Chromosomal stability|
Because many of the syndromes described above are rare, few clinical trials have been conducted in these specific populations. However, valuable information has been developed from the clinical management experience related to skin cancer risk and treatment in the XP population. Strict sun avoidance beginning in infancy, use of protective clothing, and close clinical monitoring of the skin are key components to management of XP. Full-body photography of the skin, conjunctivae, and eyelids is recommended to aid in follow-up. Although few studies on treatment of SCC in the XP population have been done, in most cases treatment is similar to what would be recommended for the general population. Actinic keratoses are treated with topical therapies such as 5-fluorouracil (5-FU), cryotherapy with liquid nitrogen, or dermabrasion, whereas cutaneous cancers are generally managed surgically.