Cutaneous lipomas and macrocephaly as early signs of PTEN hamartoma tumor syndrome

Abstract

Superficial lipoma is a painless, soft subcutaneous mass that develops slowly and results from benign proliferation of mature adipocytes. 1 It accounts for approximately 5% of soft-tissue tumors in children. 2 Most are localized in the neck, trunk, or upper thighs. Lipomatosis, defined by an abnormal deposition of fat tissue or multiple lipomas, is rare in children and has been associated with Bannayan-Riley-Ruvalcaba syndrome or Cowden syndrome. 2,3 These two genetic syndromes are characterized by a phosphatase and tensin homologue (PTEN) gene mutation and are now unified into the single entity, PTEN hamartoma tumor syndrome (PHTS). 4 Macrocephaly with developmental delay (DD), intellectual disability (ID), or autism spectrum disorder (ASD) are the most common presenting signs in childhood, but dermatological findings are often present at diagnosis. 5-7 Here, we report 13 cases of PHTS in children and teenagers, all initially presenting cutaneous lipoma(s) and macrocephaly. Early diagnosis of this syndrome is important because of the increased risk of malignant tumors and the frequency of neurologic disorders or learning difficulties.

PTEN hamartoma tumor syndrome: Clinical and genetic characterization in pediatric patients

“…Macrocephaly is a major sign in PHTS. All our patients presented macrocephaly, as it has been reported in several other cohorts [ 5 , 20 ]. Seventy-eight percent of our sample (7/9) had a head circumference SD score over + 4, greater than a French cohort and similar to an Italian cohort, which are the studies closest to the Spanish population [ 5 , 20 ].…”

Bannayan‐Riley‐Ruvalcaba syndrome with gingival hyperpigmentation and facial papules

“…As such, children often do not meet PHTS diagnostic criteria without a suggestive family history, which may delay their diagnosis. While penile macules may be one of the primary physical finding pointing to a diagnosis of BRRS, recent studies raise new criteria for consideration 2 . We offer the association of gingival hyperpigmentation and diffuse, facial, and ear angiofibromas as a potential expansion to the BRRS and pediatric PHTS clinical presentation.…”

“…While penile macules may be one of the primary physical finding pointing to a diagnosis of BRRS, recent studies raise new criteria for consideration. 2 We offer the association of gingival hyperpigmentation and diffuse, facial, and ear angio-…”

“…PTEN hamartoma tumor syndrome (PHTS) is a spectrum including Cowden syndrome (CS) and Bannayan‐Riley‐Ruvalcaba syndrome (BRRS), considered to be allelic variants with distinct phenotypes 1 . The CS phenotype prevails in adulthood 2 and is characterized by mucocutaneous lesions (trichilemmomas, palmar keratoses, papillomatous papules), macrocephaly, and increased predisposition to thyroid, breast, and endometrial cancers 3 . BRRS, the pediatric variant, is associated with macrocephaly, lipomas, hemangiomas, penile pigmented macules, vascular anomalies, and developmental delay.…”

The Skin in Cowden Syndrome

“…Histology of penile macules from a patient with BRRS showed hyperplasia of the epidermis with increased pigment in the basal layer and slight increase in the number of melanocytes ( 47 ). In a case series of children with PTHS, genital lentiginosis was found in all patients with genital evaluation as early as age 2.5 years ( 58 ). A study of patients with PTEN mutations from 1 to 26 years found that penile macular pigmentation was present in 41% of males in the cohort, with earliest report of pigmentation occurring at 15 months of age ( 57 ).…”