Clinical Pearls: Disorders With Malignant Potential

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Basal Cell Nevus

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The syndrome is caused by gene defects that regulate growth and differentiation; mutations in the PTCH gene impair the PTCH protein inhibition of SMOOTHENED (SMO), a transmembrane protein. SMOs active signaling contributes to tumor forma¬tion ... Clues to the diagnosis in early life include a family history, frontal bossing, and hypertelorism ... Cleft lip and palate may be associated ... BCCs begin in early childhood, and are often small, banal appearing monomorphic, brown, smooth dome shaped papules, very acrochordon like, and not looking like typical adult BCC's at all ...

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Basal Cell Nevus

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Learning difficulties are common ... A pediatric dentist should be part of the care team ... Photoprotection is important, and should include sun¬protective garments, hats, and broad spectrum sunscreens ... X rays and radiotherapy should be avoided ... Consider topical imiquimod as a treatment option

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Xeroderma Pigmentosum XP

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XP is caused by gene mutations responsible for the repair of UV induced DNA damage, which involves recognition of damaged DNA, unwinding of the DNA by helicase, and incision and removal of injured DNA strands by enclonucleases; each step has mutations associated with one or several complementation groups ... Photosensitivity in infants can show up as crying on sun exposure ... Families shouldn't make their life adjustments alone; the XP support group and website www.xps.org, is invaluable in keeping "state of the art" with XP care ... Sunprotec¬tive garments or UV suits, window tinting, and UV meters are important parts of care, along with constant broad spectrum sunscreen, to be worn inside and out

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Xeroderma Pigmentosum

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Children may be tutored at home, although we have been able to accommodate classrooms with UV filters and set up special programs ... Consider developmental delay, and refer early for evaluation and management ... Vigilant cancer screening is crucial, and serial photography is very useful to track changing skin lesions ... "Camp Sundown" is a must it is a camp dedicated to sun sensitive children and their families

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Muir-Torre

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Ophthalmic sebaceous tumors may be a presenting sign ... Sebaceous adenoma or carcinoma should prompt a trip to an internist for a screening evaluation, looking for visceral malignancies ... Sebaceous hyperplasia and sebaceous epitheliomas arising witin nevus sebaceous of jaclassohn are not part of the syndrome ... The associated visceral malignancies may be indolent, and detection can lead to prolonged survival ... Both hereditary nonpolyposis colorectal cancer and Muir Torre syndrome are caused by inherited DNA mismatch repair defect ... Mutations in the MSH2 gene located on 2p are commonly implicated, while mutations in the MSH1 gene located on 3p, can also cause the syndrome

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Dyskeratosis Congenita

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Dyskeratosis congenita is caused by inherited defects in the telomerase complex ... Autosomal dominant clyskeratosis congenita is associated with mutations in the RNA component of telomerase, hTERC, while X linked clyskeratosis congenita is caused by mutations in the gene encoding dyskerin, a protein implicated in both telomerase function and ribosomal RNA processing ... X linked dyskeratosis congenita is clearly the most common ... X linked recessive and autosomal recessive cases have a high incidence of nail dystrophy, skin changes and leukoplakia, with earlier pre¬sentation (median is approximately 15 years) ... Autosomal dominant cases are usually milder, and may present later (median age at diagnosis, 28 years)

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Dyskeratosis Congenita

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Some patients may be thought to have twenty nail dystrophy; pigmentary and mucosal changes are sufficient to make the differentiation ... Bone marrow dysfunction can be the first manifestation ... Mucosal surfaces should be followed carefully with liberal biopsies of any worrisome changes ... Hematopoietic stem cell transplantation is the standard treatment of bone marrow complications; nonmyeloablative conditioning regimens may be more successful.

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Gardner

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Gardner syndrome is caused by mutations in the adenomatous polyposis of the colon gene (APQ ... CHRPE is very useful marker for the disease ... Children at risk as a result of family history may be followed early with eye examinations, stool guaics, and sigmoidoscopy ... Annual sigmoicloscopy is advised beginning at age 12 years, and total colectomy may be needed ... Nonsteroidal anti inflammatory drugs (NSAIDs) and cyclooxygenase 2 inhibitors have been used to try to decrease polyps or colorectal cancer, but I would check new studies to see if these medications are really considered useful....

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Gardner

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When a patient presents with multiple epider¬moid cysts, it should prompt eliciting a family history of polyps and/or colonic can¬cer ... Gastroenterology, general surgery, oral surgery, radiology, ophthalmology, endocrinology and neurology are all appropriate specialties to assist with care

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Peutz Jeghers

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The disorder is caused by mutations in the serine/threonine kinase STU I gene ... The pigmented macules on the lips are very amenable to treatment with ruby or Alexandrite lasers ... We coordinate laser treatment with endoscopy, utilizing the sedation/anesthesia to make the laser "painless" . . . Endoscopy should be routine, with removal of polyps to minimize bowel wall invasion ... For history buffs, Keller et a]. (Familial Cancer 2002;1:181 185) reviews the history of Peutz Jeghers syndrome, including biographic information about Jan Peutz and Harold Jeghers.

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Cowden

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PTEN mutations are responsible for Cowden syndrome ... There is overlap with Ban nayan Ri ley Ruvalcaba syndrome, and cancer surveillance is appropriate for pa¬tients with both syndromes ... Patients usually present in their 30s or 40s, while breast disease in women may be seen in their 20s ... Breast cancer has been reported in males as well ... Laser vaporization of trichilemmomas may be useful for cosmetic improvement ... The most important intervention is excellent screening for malignancies by an internist

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MEN Type IIb

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Both MEN llB and IIA are caused by mutations in the RET proto oncogene ... Thick, full lips can be noticed first, and peclunculated neuromas can occur on the tongue and eyelids as welI ... Diagnosis is often made in early teenage years ... Neuromas are not usually bothersome ... Medullary thyroid carcinoma can occur very early in life, and some experts recommend treatment even in the first 6 months of life!

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Birt-Hogg-Dube

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Birt Hogg Dube is a syndrome caused by mutations in the gene encoding folliculin . . . The three tumors initially associated with this syndrome fibrofolliculoma ' trichodiscoma, and acrochordon are all apparently variations of fibrofolliculomas ... Multiple firm papules, 2 to 4 mm, on the face, neck, and/or trunk, with or without soft pedunculated achrocordon like lesions should raise clinical suspicion . . . Lesions usually occur after age 25 . . .

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Birt-Hogg-Dube

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Specific history should be elicited including pulmonary disease (including recurrent spontaneous pneumothorax, lung cysts, and/or bullous emphysema) and renal malignancy . . . BHDS is autosomal dominant, so screening abdominal CT and renal ultrasound should be done for patients and at risk relatives ...