A 68 year-old patient presented with complaints of pigmentation on his fingers, fingernails, and lips for the past year. A recent upper and lower gastrointestinal endoscopy was normal.The patient had no relevant family history. He was otherwise healthy.
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Laugier-Hunziker syndrome (LHS) is a rare benign condition characterized by diffuse macular hyperpigmentation of the oral mucosa and lips. LHS is frequently associated with longitudinal melanonychia and genital melanosis. The pathogenesis is unknown, although there is no malignant potential or underlying systemic abnormalities associated with LHS.
LHS should be considered in the differential diagnosis of a patient presenting with adult-onset mucocutaneous and nail hyperpigmentation in the absence of systemic manifestations. Since LHS is a benign condition that shares many features with other mucocutaneous pigmentary disorders, it is important to rule out the diseases that require medical intervention.
Patients with LHS present with multiple flat, smooth, gray to brown-black lenticular macules ranging in size from 2-5mm in diameter on the oral mucosa and lips. Less frequently, hyperpigmented lesions may also appear on the neck, chest, abdomen, esophagus, sclera, genitals, and perianal region.
The hyperpigmentation occurs spontaneously and is gradually acquired after puberty with no tendency to regress. In over half of LHS cases, the pigmentation affects the fingernails or toenails as a single longitudinal band of varying width and intensity; pigmentation of the proximal nail fold may be present with melanonychia.
Muir-Torre syndrome (MTS) is an autosomal dominant disorder characterized by sebaceous neoplasms, keratoacanthomas and internal malignancies. MTS is a phenotypic variant of Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer. In over half of individuals with MTS, visceral malignancy precedes the appearance of cutaneous lesions.
The most specific marker for MTS is the sebaceous adenoma, which presents as a yellow papule or nodule predominantly on the central face, but may also be found on extrafascial sites.
Other skin manifestations observed in MTS include multiple keratoacanthomas. The most common internal malignancy found in individuals with MTS is colon cancer, followed by genitourinary cancers, breast cancer, and hematologic disorders. The most prominent mutation associated with MTS occurs in the DNA mismatch repair gene MSH2. Careful cancer surveillance with colonoscopy and regular dermatologic follow-up is recommended for MTS patients.
Cowden syndrome (CS), also known as multiple hamartoma syndrome, is a rare autosomal dominant heritable cancer syndrome with variable expression in multiple organ systems. It is characterized by hamartomatous neoplasms of ectodermal, mesodermal, and endodermal origin.
In CS, hamartomas are found in almost all organs (<5mm in size). They are predominantly on the skin, mucosa and gastrointestinal tract. Over 90% of individuals with CS have macrocephaly and pathognomonic skin manifestations by the time they are in their late 20s.
Mucocutaneous features commonly seen in CS include trichilemmomas, oral papillomatosis, acral keratosis, and palmoplantar keratosis. Trichilemmomas are flesh-colored warty papules that appear around the eyes, nostrils, and mouth.
Many CS patients present with numerous white papules on the buccal and gingival mucosa that become confluent to give a cobblestone-like appearance in the oral cavity. CS occurs due to germline mutations in the tumor suppressor gene PTEN. Patients with CS are at increased risk to develop cancers of the thyroid, breast, and endometrium.
Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder characterized by hamartomatous polyps in the gastrointestinal tract and pigmented mucocutaneous macules (lentigines) on the lips and buccal mucosa.
Gastrointestinal polyps found in PJS develop in the first decade of life. Over half of PJS patients experience gastrointestinal complications such as abdominal pain, rectal bleeding, and anemia before the age of 20. PJS patients have an increased lifetime risk of developing intestinal malignancies such as colorectal cancer, in addition to carcinomas of the stomach, pancreas, lungs, breasts, and ovaries.
PJS is the most important differential diagnosis of LHS. LHS shares some clinical features with PJS, but LHS lacks familial history and systemic involvement like hamartomatous gastrointestinal polyposis.
Julie Ngyuen is a medical student at Baylor College of Medicine.
Adam Rees, MD, a graduate of the David Geffen School of Medicine at UCLA, practices dermatology in Los Angeles.
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