Proteus Syndrome

Background

Some of the clinical features, such as subcutaneous masses, may occur at any site of the body; however, other findings are dependent on involvement of specific sites, such as cranial exostosis. Some of the major clinical features:

Hemihypertrophy (partial or complete)
Macrodactyly
Subcutaneous masses (lipomatous, hemangiomatous, lymphangiomatous, and hybrid tumors)
Plantar or palmar masses (connective tissue nevi or lipomas)
Exostoses (cranial or distal)
Epidermal nevus (linear or whorled)
Scoliosis

The First National Conference on Proteus Syndrome found the most important diagnostic criteria include:

Mosaic distribution of lesions
Progressive course
Sporadic occurrence
Connective tissue nevus
Epidermal nevus
Disproportionate overgrowth (limbs, skull, external auditory meatus, vertebra, or viscera)
Specific tumors
Dysregulated adipose tissue (lipomas, lipoatrophy)
Vascular malformation, and facial phenotype

PATHOGENESIS CHARACTERIZATION

Possible somatic mutation
The cause of Proteus syndrome is unknown, and no specific gene mutation has been identified

Underlying defect may be a somatic mutation, lethal in the nonmosaic state, that affects receptors, with subsequent alteration in local production and regulation of tissue growth factors

CLINICAL VARIANTS CHARACTERIZATION

Genital Tract Tumors in Proteus Syndrome: Report of a Case of Bilateral Paraovarian Endometrioid Cystic Tumors of Borderline Malignancy and Review of the Literature

Rajeeva R. Raju, M.D, William R. Hart, M.D., David K. Magnuson, M.D., Janet R. Reid, M.D. and Douglas G. Rogers, M.D.

Departments of Anatomic Pathology (RRR, WRH), Pediatric Surgery (DKM), Pediatric Radiology (JRR), and Pediatric and Adolescent Endocrinology (DGR), The Cleveland Clinic Foundation Cleveland, Ohio

Mod Pathol 2002;15:172-180 Abstract quote

Proteus syndrome is a rare, sporadic disorder that causes postnatal overgrowth of multiple tissues in a mosaic pattern. Characteristic manifestations include: overgrowth and hypertrophy of limbs and digits, connective tissue nevus, epidermal nevus and hyperostoses. Various benign and malignant tumors and hamartomas may complicate the clinical course of patients with the syndrome. Commonly encountered tumors include hemangiomas, lymphangiomas and lipomas. Tumors of the genital tract occur less often. Bilateral ovarian cystadenomas are regarded as having diagnostic value in Proteus syndrome when occurring within the first two decades of life.

We describe a 3-year-old girl with Proteus syndrome who developed bilateral paraovarian villoglandular endometrioid cystadenomatous tumors of borderline malignancy (low malignant potential) of the broad ligament. Desmoplastic tumor implants, presumably noninvasive, were present in biopsies from the pelvic floor, cul-de-sac and omentum. This is the first recognized example of a cystic borderline epithelial tumor of the female genital tract and the first paraovarian tumor reported in a patient with Proteus syndrome. Previously reported tumors and cystic lesions involving the female genital tract and the male genital tract in patients with Proteus syndrome are reviewed.

We suspect that specific testicular and paratesticular tumors may prove to have the same diagnostic value in Proteus syndrome as do bilateral cystic ovarian and paraovarian tumors.

Pediatr Dermatol. 1994;11:222-226
Eur J Pediatr. 1983;140:5-12
Arch Dermatol. 1989;125:1109-1114

Commonly Used Terms

Congenital and Metabolic Disorders

Last Updated 3/15/2002