Rahul B. Chaudhari, MD, MRCP, Hongxing Gui, MD, Jigisha Chaudhari, MD, Ihab Lamzabi, MD; University of Pennsylvania Health System, Philadelphia, PA
Introduction: Cowden syndrome (CS), also known as PTEN hamartoma syndrome is an autosomal dominant disorder with multiple hamartomas involving organs derived from all three grem cell layers. The overall prevelance of Cowden syndrome is 1 per million. It has an increased predisposition to colorectal cancer. Gastrointestinal (GI) polyps of various histologic types including hyperplastic polyps, ganglioneuromas and hamartomatous polyps have been reported in 35-85% CS patients, with ganglioneuromas considered the most specific GI finding. Intramucosal lipomas have been recently reported associated with CS. However, the significance of intramucosal lipomas, compared to ganglioneuromas, in predicting CS have not yet been fully characterized. Methods: We conducted a retrospective study enrolling 55 patients with either intramucosal lipomas or ganglioneuromas in GI polyps biopsied during 2010-2019 (over 70,000 cases). A total number of 190 polyps from those patients were reviewed. Results: We identified 15 patients having germline PTEN mutation or clinical CS. Among those, nine patients (9/15) had 13 intramucosal lipomas and six (6/15) had 13 ganglioneuromas. Of 40 patients without CS, 12 patients (12/40) had 14 intramucosal lipomas and 22 patients (22/40) had 30 ganglioneuromas. Forty-eight percent 48% (13/27) intramucosal lipomas were associated with CS versus 30% (13/43) of ganglioneuromas. Three CS patients had both intramucosal lipoma and ganglioneuroma, which was not seen in patients without CS. In addition, four CS patients (4/15, 27%) had two intramucosal lipomas while only one patient without CS (1/40, 2.5%) had more than one lipoma. Discussion: Intramucosal lipomas are uncommon and easily overlooked by clinicians and pathologists, despite their diagnostic significance for Cowden syndrome (PTEN hamartoma tumor syndrome), an inherited multiorgan cancer syndrome. Clinical features remain the cornerstone of diagnosis as only 25–35% of patients harbor identifiable PTEN mutations. Our data provide evidence that intramucosal lipomas are important harbingers of Cowden syndrome. It is more common in CS than ganglioneuroma and has a higher value in predicting CS in our study. Presence of both intramucosal lipomas and ganglioneuromas or multiple intramucosal lipomas is highly specific for CS. Gastrointestinal pathologists, gastroenterologists, and geneticists should increase their awareness of this subtle but diagnosable lesion strongly associated with Cowden syndrome in order to screen for CS.
Figure 1. (A, C) Intramucosal lipoma in CS. (B, D) Ganglioneuroma in CS
Disclosures: Rahul Chaudhari indicated no relevant financial relationships. Hongxing Gui indicated no relevant financial relationships. Jigisha Chaudhari indicated no relevant financial relationships. Ihab Lamzabi indicated no relevant financial relationships.