Background: Hereditary hemorrhagic telangiectasia (HHT), also called Osler–Weber–Rendu syndrome, is an autosomal dominant disease characterized by aberrant blood vessel development throughout the body that results in telangiectasias, arteriovenous malformations (AVMs), and arteriovenous fistulas. Pathogenic variants in multiple genes can cause HHT, with three major disease associated genes, one of which is SMAD4. HHT caused by mutations in SMAD4 is also associated with juvenile polyposis syndrome (JPS), a condition termed JPS-HHT. Histologic features of HHT polyps have not been well characterized other than their non-adenomatous nature. Here we attempt to characterize the histologic features of such polyps in this typical case of JPS-HHT. Design: A case report of a 17-year-old female with a history of intermittent rectal bleeding and a family history of JPS underwent genetic testing which was positive for SMAD4 mutation. She was diagnosed with Juvenile polyposis syndrome and SMAD4- deficient HHT evidenced by multiple colonic polyps with histologic confirmation in the past 6 years, and pulmonary AVMs detected by echocardiogram. In a recent surveillance colonoscopy, a new 15 x 7 mm pedunculated sigmoid colon polyp with a 5 x 4 mm stalk was identified and removed. Results: Histologic examination of the polyp revealed a non-adenomatous polyp with hyperplastic colonic glands composed of hyperplastic and hypertrophic epithelia. The polyp was remarkable for abnormal vasculatures in three patterns: 1) Telangiectasia to various extents unrelated to mucosal erosion (Fig.1- A, B), 2) Focal AVMs (Fig. 1- C), and 3) Direct juxtaposition of the abnormal vasculatures immediately beneath the epithelial lining (Fig.1 B, C). The polyp lacked a prominent central thick-walled feeding vessel characteristic of the ordinary hyperplastic polyp. Immunohistochemistry revealed a complete loss of SMAD4 in the glandular epithelia but not in blood vessels (Fig. 1- D).
Elzieny M, Pokharel A, Qu ZH. A case of hereditary telangiectasia with juvenile polyposis syndrome associated with SMAD4 mutation. Lab Invest. 2023 Mar;103(3 Suppl.1):S1579-S1580. doi:10.1016/j.labinv.2023.100100