5. pigmented lesions part 3

what are the seven developmental melanin-associated pigmented lesions?

• McCune Albright syndrome

• Neurofibromatosis I

• Carney complex

• Peutz-Jeghers syndrome

• Leopard syndrome

• dyskeratosis congenita

• Laugier Hunziker syndrome

which developmental melanin-associated pigmented lesion?

• variant of polyostotic fibrous dysplasia: developmental condition resulting from GNAS1 mutation

• associated w café au lait (light brown) macules and endocrinopathies

McCune-Albright

GNAS1 mutation which developmental melanin-associated pigmented lesion?

McCune-Albright syndrome

what is the triad of McCune-Albright syndrome?

• polyostotic fibrous dysplasia affecting several bones (not just maxilla and mandible)

• endocrine dysfunction: hyperthyroidism and/or sexual precocity, the latter predominantly identified in female

• cutaneous hyperpigmentation (café au lait)

fibrous dysplasia affecting maxilla

GNAS1 gene mutation 

what is neurofibromatosis?

• autosomal dominant NF1 gene mutation mapped to chromosome 17

• aka Von Recklinghausen disease

• specific diagnostic criteria 

• neurofibromas are benign tumors that grow on nerves (MAS does not have)

NF1 gene mutation

neurofibromatosis

what are the diagnostic criteria for neurofibromatosis?

two or more of the following:

• 6⁺ café au lait spots

  • >5mm prepubertal pts

  • >15 mm in postpubertal pts

• 2+ neurofibromas or one plexiform neurofibroma

• axillary and/or inguinal freckling

• optic nerve glioma

• distinctive osseous lesion like dysplasia of sphenoid wing, thinning of long bone cortex w or w/o pseudoarthritis

• first-degree relative (parent, sibling, offspring) w NF1 according to above criteria

neurofibromatosis I

neurofibromatosis neurofibromas have propensity to turn into what type of cancer?

soft tissue cancer (vs someone w sporadic neurofibroma)

what’s the dermatological/geographical difference between neurofibromatosis and McCune Albright?

McCune-Albright café au lait has irregular edges like coast of Maine while neurofibromatosis café au lait has smooth border like coast of cali

which of the following is not characteristic of neurofibromatosis?

A. Unilateral enlargement of tongue

B. Lisch nodules

C. Café au lait macules

D. Autosomal recessive

E. Optic glioma

D. autosomal recessuve

which developmental melanin-associated pigmented lesion?

• autosomal dominant 

• cardiac myxomas

• cutaneous myxomas

• spotty pigmentation: lentigines on face and vermillion border, blue nevi including epithelioid blue nevi 

carney complex

myxomas

benign, non-cancerous tumor made of gelatinous connective tissue, most commonly found in the heart, but also in other soft tissues

Carney complex

lentigines

small, flat, pigmented spots on the skin that are a result of excess melanin production and are commonly known as age spots, sunspots, or liver spots

Carney complex

nevus

mole, a small, typically benign skin growth

Carney complex

autosomal dominant developmental melanin-associated pigmented lesion? (hint)

neurofibromatosis, carney complex, and peutz-jegher

PRKAR1A gene located at 17q22-24 but no targeted Tx yet

Carney complex

carney complex (C = lentigines)

a biopsy of this would look like melanotic macule

which developmental melanin-associated pigmented lesion?

• autosomal dominant 

• mutation of STK11/LKB1 gene 

• Freckle-like lesions of the hands, peri-oral region, and/or oral mucosa

• Intestinal polyposis with predisposition to adenocarcinoma (super young adults)

Peutz-Jegher

mutation of STK11/LKB1 gene

Peutz-Jegher

Peutz-Jeghers

what are the four diagnostic criteria for Peutz-Jeghers?

• 3⁺ histologically confirmed Peutz Jeghers polyps

• any number of Peutz-Jeghers polyps w a family history of the syndrome

• characteristic prominent mucocutaneous pigmentation w a family history

• any number of Peutz-Jeghers polyps and characteristic prominent mucocutaneous pigmentation

Peutz-Jegher

mutation of PTPN11 gene

leopard syndrome

leopard syndrome

what does leopard of leopard syndrome stand for?

Lentigines

ECG conduction abnormalities

Ocular hypertelorism

Pulmonic stenosis

Abnormal genitalia

Retardation of growth

Deafness

DKC1 gene mutation

dyskeratosis congenita

relevant to white lesion lecture, 30 yo w (pre)cancer diagnosis

dyskeratosis congenita

which developmental melanin-associated pigmented lesion: rare inherited disorder characterized by premature aging of certain tissues and organs?

dyskeratosis congenita

which developmental melanin-associated pigmented lesion?

• Rare acquired, diagnosis of exclusion

  • Macules of the labial and/or buccal mucosa

  • Longitudinal streaks in fingernails (melanonychia)

Laugier Hunziker

Laugier-Hunziker syndrome

Laugier Hunziker syndrome

Which of the following conditions does an individual appear to have with oral melanotic macules and gastrointestinal polyps?

A. Addison disease

B. Laugier Hunziker syndrome

C. Peutz-Jegher syndrome

D. McCune-Albright syndrome

C. Peutz-Jegher syndrome