Temporal Evolution and Management of Fast Flow Vascular Anomalies in PTEN Hamartoma Tumor Syndrome

Abstract

Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is characterized by formation of recurrent benign tumors described as PTEN hamartoma of soft tissue that may contain fast flow vascular anomalies (FFVA). The purpose of this study is to review the temporal evolution and management of FFVA in PHTS. A retrospective review of 22 patients (9 males), age 1 to 18 (median 9) years diagnosed with PHTS at a tertiary care pediatric hospital between October 2002 and August 2017 revealed 4 patients with FFVA. Imaging, management, and treatment complications were reviewed. During median follow-up of 8 (range: 4–13) years, ultrasound and magnetic resonance imaging performed for recurrent pain, showed progressive increase in the size of hamartomas and development of new FFVA in three-fourth patients. Medical management included pain medications, oral sirolimus, and physical and psychiatric therapy. Surgical excision of hamartoma (n = 1) resulted in recurrence within 3 months. Between 4 and 24 (average 1.5/year) embolizations were performed per patient. Pain related to FFVA responded well to embolization. Pain secondary to PTEN hamartoma responded poorly to percutaneous sclerosant injection, but demonstrated improvement with sirolimus. There was no correlation between serum sirolimus levels and frequency/timing of recurrence of FFVA/hamartoma. Complications included sclerosant migration into digital arteries (n = 1), subclavian vein stenosis due to glue migration (n = 1), oral mucositis (n = 4), and elevated triglycerides (n = 4). Patients with PHTS present with recurrent pain requiring life-long management with a multi-disciplinary team. Pain due to FFVA responds to embolization, and pain due to hamartoma responds to sirolimus. This improves quality of life, but does not prevent disease progression.

Keywords

PTEN Hamartoma Tumor Syndrome - PTEN hamartoma of soft tissue - vascular anomaly - arteriovenous malformation - sirolimus - embolization - sclerotherapy

Disclosures

None of the authors has any disclosures.

• References

• 1 Hobert JA, Eng C. PTEN hamartoma tumor syndrome: an overview. Genet Med 2009; 11 (10) 687-694
• 2 Eng C. PTEN: one gene, many syndromes. Hum Mutat 2003; 22 (03) 183-198
• 3 Ngeow J, Sesock K, Eng C. Clinical implications for germline PTEN spectrum disorders. Endocrinol Metab Clin North Am 2017; 46 (02) 503-517
• 4 Pilarski R, Burt R, Kohlman W, Pho L, Shannon KM, Swisher E. Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria. J Natl Cancer Inst 2013; 105 (21) 1607-1616
• 5 Roche AF, Mukherjee D, Guo SM, Moore WM. Head circumference reference data: birth to 18 years. Pediatrics 1987; 79 (05) 706-712
• 6 Kurek KC, Howard E, Tennant LB. , et al. PTEN hamartoma of soft tissue: a distinctive lesion in PTEN syndromes. Am J Surg Pathol 2012; 36 (05) 671-687
• 7 Chism CB, Crawford L, Tchakarov A, Al-Ibraheemi A, Beckmann NM. PTEN hamartoma of the soft tissue: the initial manifestation of an underlying PTEN hamartoma tumor syndrome in a 4-year-old female. Skeletal Radiol 2017; 46 (11) 1591-1595
• 8 Tan WH, Baris HN, Burrows PE. , et al. The spectrum of vascular anomalies in patients with PTEN mutations: implications for diagnosis and management. J Med Genet 2007; 44 (09) 594-602
• 9 Iacobas I, Burrows PE, Adams DM, Sutton VR, Hollier LH, Chintagumpala MM. Oral rapamycin in the treatment of patients with hamartoma syndromes and PTEN mutation. Pediatr Blood Cancer 2011; 57 (02) 321-323
• 10 Sharabi SE, Koshy JC, Hollier Jr LH. Multiple, recurrent, refractory vascular malformations as the primary presenting feature of a PTEN mutation. Pediatr Dermatol 2011; 28 (04) 466-467
• 11 Matsuhisa A, Kishino M, Nakadate M, Kudo T, Inoue Y, Tateishi U. Embolosclerotherapy by the transvenous approach for lower extremity arteriovenous malformation in Cowden syndrome: a case report. Ann Vasc Dis 2016; 9 (01) 66-69
• 12 Takaya N, Iwase T, Maehara A. , et al. Transcatheter embolization of arteriovenous malformations in Cowden disease. Jpn Circ J 1999; 63 (04) 326-329
• 13 Johnson CM, Navarro OM. Clinical and sonographic features of pediatric soft-tissue vascular anomalies part 2: vascular malformations. Pediatr Radiol 2017; 47 (09) 1196-1208
• 14 Turnbull MM, Humeniuk V, Stein B, Suthers GK. Arteriovenous malformations in Cowden syndrome. J Med Genet 2005; 42 (08) e50
• 15 Cho SK, Do YS, Shin SW. , et al. Arteriovenous malformations of the body and extremities: analysis of therapeutic outcomes and approaches according to a modified angiographic classification. J Endovasc Ther 2006; 13 (04) 527-538
• 16 Gilbert P, Dubois J, Giroux MFSG, Soulez G. New treatment approaches to arteriovenous malformations. Semin Intervent Radiol 2017; 34 (03) 258-271