chapter  24
48 Pages

Genodermatoses related to malignancy

Clinical findings ● Multiple basal cell carcinomas appearing as smooth, flesh-colored to red-brown papules distributed mainly on the face, neck, back and chest (90%) (Figures 24.1-24.4)

Figure 24.1 ● Palmar and plantar pits 2-3 mm in diameter in 65-80% of patients (Figure 24.5) ● Facial milia and epidermal cysts on the limbs and trunk (-50%) (Figure 24.6) ● Occasionally acrochordons (Figure 24.7)

Extracutaneous manifestations ● Odontogenic cysts of the jaw in about 80% of patients: multiple, often symptomatic,

causing marked tooth displacement ● Calcification of falx cerebri in about 85% of patients ● Musculoskeletal abnormalities: enlarged occipitofrontal circumference (80%), frontal bossing (65%), fused or bifid ribs (50%), spina bifida occulta of cervical or thoracic

(15-45%), cleft palate (5%), polydactyly (4%)

Figure 24.2

Figure 24.3

Figure 24.4

Figure 24.5 ● Eye anomalies in 10-25% of patients: cataract, strabismus, colobomas of iris, choroid

or optic nerve, hypertelorism ● Hypogonadism in 5-10% of male patients

Figure 24.6

Figure 24.7 ● Kidney anomalies (5%): horseshoe kidney, unilateral renal agenesis ● Occasionally, mental retardation and seizures due to cerebellar medulloblastoma in 3-

5% that may be the first manifestation of the disease

● Cardiac fibroma (3%) ● Mesenteric cysts ● Fetal rhabdomyoma, fibrosarcoma, leiomyomas

Course and prognosis

● Basal cell carcinomas may increase in number and become aggressive after puberty ● Odontogenic cysts occur frequently before basal cell carcinomas and may easily recur

after removal ● Musculoskeletal abnormalities may be congenital and medulloblastoma may occasionally be the first manifestation

Laboratory investigations

● Histopathologic findings: typical aspect of basal cell carcinoma or rarely of infundibulocystic basal cell carcinoma

● Skeletal radiography ● Total body magnetic resonance imaging

Genetics and pathogenesis

● Autosomal dominant inheritance ● The responsible gene, the PTCH gene, is mapped to chromosome 9q22.3-q31 ● The PTCH gene is a tumor suppressor gene and patients with mutations in this gene have a predisposition not only for multiple basal cell carcinomas but also for other tumors and skeletal abnormalities

Differential diagnosis

● Bazex syndrome ● Other cancer-related genodermatoses

Follow-up and therapy

● Close surveillance is mandatory, with periodic radiography and nuclear magnetic resonance examinations

● It is necessary to avoid sun exposure and radiotherapy ● Basal cell carcinomas: topical 5-fluorouracil or imiquimod cream, surgical excision,

electrodesiccation, CO2 laser, photodynamic therapy, oral retinoids

Boutet N, Bignon YJ, Drouin-Garraud V, et al. Spectrum of PTCH1 mutations in French patients with Gorlin syndrome. J Invest Dermatol 2003; 121:478-81

Chiritesen E, Maloney ME. Acrochordons as a presenting sign of nevoid basal cell carcinoma syndrome. J Am Acad Dermatol 2001; 44:789-94

Cohen MM Jr. Craniofacial anomalies: clinical and molecular perspectives. Ann Acad Med Singapore 2003; 32:244-51

Gorlin RJ. Nevoid basal cell carcinoma syndrome. Dermatol Clin 1995; 13:113-25 Olivieri C, Maraschio P, Caselli D, et al. Intersitial deletion of chromosome 9, int del(9)

(9q22.31.2), including the genes causing multiple basal cell nevus syndrome and Robinow/ brachydactyly 1 syndrome. Eur J Pediatr 2003; 162:100-3

MUIR-TORRE SYNDROME

Synonym ● Torre syndrome

Age of onset ● Fourth or fifth decade of life

Clinical findings

Skin lesions ● Sebaceous gland tumors (hyperplasias, adenomas, carcinomas) presenting as yellow

papules or nodules located mainly on the face (Figures 24.8-24.10) ● Keratoacanthomas (one or more) spontaneously involuting as associated cutaneous finding (23%)

Extracutaneous features ● Colorectal cancers (53%) ● Colon polyps ● Genitourinary neoplasms (25%) ● Breast and lung tumors ● Hematologic malignancies

Course and prognosis

Visceral malignancies, usually of low grade, may precede the appearance of sebaceous tumors in 60%.