Data for this Review were identified by searches of Pubmed, Medline, and Online Mendelian Inheritance in Man with the search terms “familial cancer”, “cutaneous and hereditary”, “hereditary non-polyposis colorectal cancer”, “Lynch syndrome”, “Muir-Torre syndrome”, “familial polyposis”, “hamartoma syndromes”, “Peutz-Jerghers syndrome”, “Birt-Hogg-Dube syndrome”, “hereditary leiomyomatosis renal-cell carcinoma”, “familial renal cancer”, “tuberous sclerosis”, chromosome and kidney”, “Gorlin
ReviewLessons from the skin—cutaneous features of familial cancer
Introduction
This Review outlines several important familial cancer syndromes in which cutaneous features form part of the clinical diagnostic criteria. Many of the familial cancer syndromes are recognised by so-called high-risk features, including a cluster of relatives within the patient's family who have the same or similar cancers, the development of cancer at a young age, the presentation of more than one tumour, either synchronous or metachronous, or more than one tumour within a specific group of tumours that are features of a syndrome. However, several familial cancer syndromes have additional non-malignant cutaneous features, which serve as the vital clue for a clinical diagnosis (figure 1).1, 2, 3 Many of these conditions occur as the result of a de-novo mutation and present without a family history. The role of the genetic counsellor and clinical geneticist in this setting can be useful to elucidate the significance of clinical signs. Cutaneous features can be present in many familial cancer syndromes, but this Review is restricted to conditions where a diagnosis is often delayed until the proband presents to a medical oncologist in adulthood. Focus is made on naevoid basal-cell carcinoma syndrome; syndromes predisposing to colorectal cancer; syndromes predisposing to renal cancer; and the endocrine-neoplasia syndromes. The cutaneous, neoplastic, and non-neoplastic features of neurofibromatosis type I and type II have been extensively reviewed elsewhere,4 and have not been described in any further detail in this Review.
Of note, some skin signs are very specific and can be easily recognised. However, many of the skin signs associated with cancer syndromes are non-specific skin coloured papules, and referral for histological examination can be an essential step towards a unifying family diagnosis.
Section snippets
Naevoid basal-cell carcinoma syndrome (Online Mendelian Inheritance in Man [OMIM] number 109400)
Naevoid basal-cell carcinoma syndrome is a clinically variable condition due to an autosomal dominantly inherited mutation in PTCH on 9q22.5 The estimated prevalence is one in 57 000 people, with a high new mutation rate.5, 6 PTCH functions as both a developmental regulator and a tumour-suppressor gene.7, 8 Consequently, naevoid basal-cell carcinoma syndrome (NBCCS; also known as Gorlin syndrome) is characterised by features involving many organs, including the skin. The diagnosis of NBCCS is
Hereditary non-polyposis colorectal cancer (OMIM 120435)
Hereditary non-polyposis colorectal cancer (HNPCC) is a familial cancer syndrome, with onset in young people, which results from mutations in one of the mismatch repair genes.13 Cellular loss of expression of MLH1, MSH2, MSH6, or PMS2 results in the accumulation of undetected and unrepaired DNA mismatches, and consequently, increased tumour formation. Individuals with a heterozygous germline mutation in one of these genes—and who therefore only have one functional copy—are at an increased risk
Birt-Hogg-Dube syndrome (OMIM 135150)
Birt-Hogg-Dube (BHD) syndrome is a variable autosomal dominant renal cancer predisposition condition due to a heterozygous mutation in FLCN which encodes folliculin. The prevalence of BHD syndrome is yet to be established. BHD is characterised by a triad of cutaneous signs including fibrofolliculomas, trichodiscomas, and acrochordons. In addition to an increased risk of renal neoplasm, BHD is associated with a wide spectrum of non-neoplastic features, including spontaneous pneumothorax and lung
Multiple endocrine neoplasia type 1 (OMIM 131100)
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome due to heterozygous MEN1 mutations on 11q13, which results in a genetic predisposition to tumours of the pituitary gland, pancreas, and parathyroid glands, and to peptic ulcer disease. About 10% of MEN1 is caused by de-novo mutations.53, 54
Facial angiofibromas occur in 88% of patients, with more than half of individuals having more than five signs.55 These angiofibromas can cross the vermilion border of the lips. The
Conclusion
Recognition of characteristic cutaneous signs and extracutaneous features (table), in addition to the history of neoplasia, will improve the diagnosis of rare familial cancer syndromes. Many of these syndromes are associated with a high mutation rate and no family history of cancer to alert the clinician to the possibility of a germline mutation, which has a 50% chance of being passed on to subsequent offspring. For the individual, this can afford a surveillance strategy, with the possibility
Search Strategy and Selection Criteria
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Colorectal family polyadenomatous diseases. What management in 2020?
2020, Journal of Visceral SurgeryCitation Excerpt :Histologically, these can be sebaceous adenomas or carcinoma. This explains the necessity of a complete dermatologic examination in case of MAP [13]. Of note, desmoid tumors are never found in association with MAP.
Familial multiple discoid fibromas: A look-alike of Birt-Hogg-Dubé syndrome not linked to the FLCN locus
2012, Journal of the American Academy of DermatologyCitation Excerpt :However, the sensitivity of mutation detection is not 100%, so well-characterized BHD families without identified FLCN mutations definitely exist. In addition to BHD the differential diagnosis may also include other diseases characterized by multiple firm facial papules with a smooth surface such as tuberous sclerosis complex (multiple facial angiofibromas), facial angiofibromas in multiple endocrine neoplasia type 1, Cowden syndrome (multiple facial trichilemmomas that usually have a keratotic surface but may be smooth surfaced, and multiple sclerotic fibromas), multiple trichoepitheliomas, basaloid follicular hamartoma syndrome, generalized hair follicle hamartoma, and possibly also Muir-Torre syndrome and syringomas.15,32,33 The most important and most difficult histologic differential diagnosis is the plywoodlike or sclerotic fibroma as mentioned before, which may be indistinguishable without clinicopathologic correlation.
Spot diagnosis
2014, New England Journal of MedicineCitation Excerpt :Familial cancer syndromes are traditionally suspected on the basis of familial clustering of tissue-specific cancers, the development of cancer at an unusually young age, or the occurrence of more than one cancer in a person. However, several familial cancer syndromes have additional cutaneous features that can be highly specific, and awareness of the importance of these signs allows prompt diagnosis and institution of appropriate surveillance (Figure 5).1,2 The diagnosis in one family member can highlight a high risk of cancer among other family members and allows them the opportunity to effectively manage this risk.
Cancer-associated genodermatoses
2022, Braun-Falco's DermatologyBenign skin tumors arising from the hair follicles and sweat glands
2020, Russian Journal of Skin and Venereal Diseases